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Prostaglandinas intracervicales para la inducción del trabajo de parto

Boulvain M, Kelly A, Irion O
Fecha de la modificación significativa más reciente: 14 de noviembre de 2007

Esta revisión debería citarse como: Boulvain M, Kelly A, Irion O. Prostaglandinas intracervicales para la inducción del trabajo de parto (Revisión Cochrane traducida). En: La Biblioteca Cochrane Plus, 2008 Número 4. Oxford: Update Software Ltd. Disponible en: http://www.update-software.com. (Traducida de The Cochrane Library, 2008 Issue 3. Chichester, UK: John Wiley & Sons, Ltd.).

RESUMEN
Antecedentes

El empleo de las prostaglandinas para la maduración cervical y la inducción del trabajo de parto data de los años setenta. El objetivo de la administración de prostaglandinas durante el proceso de inducción del trabajo de parto es lograr la maduración del útero antes de que comiencen las contracciones. Una de las vías de administración propuestas es la intracervical. A través de esta vía se dificulta la administración de las prostaglandinas, además la necesidad de exponer el cuello uterino podría causar malestar en la mujer.

Objetivos

Determinar los efectos de las prostaglandinas intracervicales en la maduración uterina durante el tercer trimestre o en la inducción del trabajo de parto comparado con el placebo o ningún tratamiento y con las prostaglandinas vaginales (excepto misoprostol).

Estrategia de búsqueda

Se hicieron búsquedas en el Registro de Ensayos del Grupo Cochrane de Embarazo y Parto (Cochrane Pregnancy and Childbirth Group) (agosto 2007) y en bibliografías de ensayos relevantes.

Criterios de selección

Ensayos clínicos que comparen el uso de prostaglandinas intracervicales para la maduración cervical o la inducción del trabajo de parto en el tercer trimestre con placebo o ningún tratamiento, o con otros métodos antes mencionados en una lista predeterminada de métodos de inducción del trabajo de parto, (prostaglandinas intracervicales, excepto misoprostol).

Recopilación y análisis de datos

Se desarrolló una estrategia para poder trabajar con el gran volumen y la complejidad de los datos de los ensayos relacionados con la inducción del trabajo de parto. Esto implicó un método de extracción de datos en dos pasos.

Resultados principales

Se incluyeron 56 ensayos (7738 mujeres).

PGE2 intracervical con placebo o ningún tratamiento: 28 ensayos, 3764 mujeres
Cuatro estudios informaron el número de mujeres que no logró el parto vaginal dentro de las 24 horas, con un aumento en el riesgo asociado con las PGE2 (riesgo relativo [RR] 0,61; intervalo de confianza [IC] del 95%: 0,47 a 0,79). Hubo una pequeña reducción, estadísticamente no significativa, en el riesgo de cesárea con el uso de PGE2 (RR 0,88; IC del 95%: 0,77 a 1,00). Este hallazgo sólo fue estadísticamente significativo en un subgrupo de mujeres con membranas intactas y cuello uterino desfavorable (RR 0,82; IC del 95%: 0,68 a 0,98). El riesgo de hiperestimulación con cambios en la frecuencia cardíaca fetal (FCF) no aumentó significativamente (RR 1,21; IC del 95%: 0,72 a 2,05). Sin embargo, el riesgo de hiperestimulación sin cambios en la FCF aumentó significativamente (RR 1,59; IC del 95%: 1,09 a 2,33.

PGE2 intracervical con PGE2 intravaginal: 29 ensayos, 3881 mujeres
El riesgo de lograr un parto vaginal dentro de las 24 horas aumentó con la PGE2 intracervical (RR 1,26; IC del 95%: 1,12 a 1,41). No hubo cambios en el riesgo de cesárea (RR 1,07; IC del 95%: 0,93 a 1,22). Los riesgos de hiperestimulación con cambios en la FCF (RR 0,76; IC del 95%: 0,39 a 1,49) y sin cambios en la FCF (RR 0,80; IC del 95%: 0,56 a 1,15) no fueron significativamente diferentes con ambos métodos de administración de PGE2. Sólo un ensayo con un tamaño pequeño de la muestra informó la opinión de las pacientes, sin diferencias entre los grupos.

PGE2 intracervical de dosis baja con PGE2 intracervical de dosis alta: dos ensayos, 102 pacientes
Los ensayos son demasiado pequeños como para aportar información útil.

Conclusiones de los autores

Las prostaglandinas intracervicales son efectivas comparadas con el placebo, aunque resultan inferiores en comparación con las prostaglandinas intravaginales.

Esta revisión debería citarse como:
Boulvain M, Kelly A, Irion O Prostaglandinas intracervicales para la inducción del trabajo de parto (Revisión Cochrane traducida). En: La Biblioteca Cochrane Plus, 2008 Número 4. Oxford: Update Software Ltd. Disponible en: http://www.update-software.com. (Traducida de The Cochrane Library, 2008 Issue 3. Chichester, UK: John Wiley & Sons, Ltd.).


RESUMEN EN TÉRMINOS SENCILLOS

Las prostaglandinas aplicadas en el cuello uterino son efectivas para iniciar el trabajo de parto, aunque son inferiores a la administración vaginal.

Durante el trabajo de parto, el cuerpo produce prostaglandinas de manera natural. Las prostaglandinas cumplen la función de preparar el cuello uterino y ayudar a dilatarlo en respuesta a las contracciones. Cuando se decide inducir el trabajo de parto y el cuello uterino todavía no está dilatado, se emplean prostaglandinas sintéticas para madurarlo antes de utilizar los fármacos que producen las contracciones (en general, oxitocinas). Una forma de aplicar la prostaglandina consiste en colocarla en el cuello uterino con una cánula durante el procedimiento de tacto vaginal. La revisión de 56 ensayos (7738 mujeres) halló que si bien esta vía de administración es efectiva, no ofrece ventajas con respecto a otros métodos de administración, en particular, la vía vaginal.


ANTECEDENTES

La inducción del trabajo de parto se efectúa hacia el final del embarazo, tanto por motivos médicos como por conveniencia. Existe controversia acerca de los posibles riesgos y beneficios de la intervención en indicaciones específicas (ver revisiones: Gülmezoglu 2006; Flenady 2002; Boulvain 2001b; Irion 1998a) o sin indicación médica. Se han realizado numerosos ensayos que comparan regímenes y vías de administración de diversos fármacos para lograr la maduración del cuello uterino y la inducción del trabajo de parto, en comparación con los escasos ensayos que evalúan las indicaciones para la inducción del trabajo de parto. Dada la frecuencia de dicha intervención, resulta importante evaluar el beneficio de la inducción del trabajo de parto en determinadas situaciones. Sin embargo, cuando se decide inducir el trabajo de parto, el objetivo es lograr un parto vaginal dentro de un período de tiempo restringido, minimizando los efectos secundarios tanto para la madre como para el recién nacido. Los principales efectos secundarios son el trabajo de parto disfuncional y la actividad uterina excesiva, y eventualmente el sufrimiento fetal; ambos llevan a la cesárea. La inducción con oxitocina se asocia con una elevada tasa de fracaso cuando el cuello uterino no está maduro. La rotura artificial de membranas, en presencia de un cuello uterino no favorable, posee una baja efectividad y probablemente resulte imposible practicarla. Los preparados de prostaglandina parecen favorecer la maduración cervical y el inicio del trabajo de parto en mujeres con cuello uterino desfavorable (Keirse 1993). En un principio se utilizó la prostaglandina F2a, luego se produjo la prostaglandina E2 y sus análogos. Recientemente se han evaluado los análogos de la prostaglandina E1 (misoprostol), y se utilizan cada vez más. La maduración cervical se logra mediante la modificación del colágeno cervical y la alteración de la concentración de glucosaminoglicanos relacionados con el cuello uterino (Huszar 1984; Rath 1993). En la actualidad, las prostaglandinas son ampliamente utilizadas en la práctica clínica, aunque se informan efectos secundarios. Éstos incluyen síntomas gastrointestinales (náuseas, vómitos, diarrea), fiebre e hiperestimulación uterina, con o sin sufrimiento fetal (Keirse 1993). Se informaron casos de rotura uterina, especialmente en pacientes con cesárea previa. (Raskin 1999; Vause 1999). Ciertos estudios de cohorte con grandes tamaños de la muestra sugieren que el riesgo de rotura uterina no se modificó con el uso de prostaglandinas (Chez 1995), mientras que otros sugieren un aumento del riesgo asociado con el empleo de prostaglandinas (RCOG 2007). Existen, o existían, numerosos preparados de prostaglandina disponibles, incluida la PGF2 alfa, la PGE2, la sulprostona (una análogo sintético de la PGE2), la PGE1 y el misoprostol (un análogo sintético de la PGE1). Se los ha utilizado por diversas vías, incluida la administración local (extraamniótica, intracervical, intravaginal) y general (oral, intramuscular e intravenosa). Los preparados de prostaglandina de administración local incluyen: gel, ya sea en un gel de triacetina estable o en un gel a base de almidón; pesarios, supositorios o comprimidos vaginales a base de lactosa. Las dosis de la PGE2 sulprostona suele ser de 0,5 mg para el uso intracervical, de 2 a 3 mg para el uso intravaginal y de 10 mg para el óvulo de liberación lenta. Sin embargo se han utilizado otros preparados y dosis de PGE2 de hasta 5 mg (Mastrogiannis 1995). También están disponibles comprimidos orales y preparados estériles de uso parenteral. En muchos centros, el análogo de la PGE1 misoprostol ha reemplazado el uso de los análogos de la PGE2 para la maduración cervical y la inducción del trabajo de parto. Sin embargo, en muchos países el misoprostol no se comercializa por lo que posiblemente no esté disponible. Por otra parte, los preparados comerciales de los análogos de la PGE2 son caros y necesitan refrigeración. Con lo cual se limita la disponibilidad en muchos centros.

La prostaglandina puede aplicarse por vía intracervical durante el tacto vaginal. Este procedimiento incluye la exposición del cuello uterino y la inserción de una cánula. Los revisores del presente estudio opinan que el procedimiento puede ocasionar cierto malestar en la paciente además de ser más dificultoso en comparación con la vía de administración vaginal. Otro posible inconveniente es la pérdida de fármaco desde el cuello uterino hacia la vagina. Por lo tanto, parte del fármaco será absorbido por vía vaginal, en una dosis inferior a la prevista (Irion 1998a).

Esta revisión es una de una serie de revisiones acerca de los métodos de inducción del parto que utiliza un protocolo estandarizado (Hofmeyr 2000). Los lectores pueden consultar las siguientes revisiones sistemáticas Cochrane para mayor información acerca de la inducción del trabajo de parto con prostaglandinas: "Prostaglandinas vaginales (PGE2 y PGF2a) para la inducción del trabajo de parto a término" (Kelly 2003); "Prostaglandinas extraamnióticas para la inducción del trabajo de parto" (Hutton 2001); "Prostaglandinas intravenosas para la inducción del trabajo de parto" (Luckas 2000); "Misoprostol oral para la inducción del trabajo de parto" (Alfirevic 2006); y "Misoprostol vaginal para la inducción del trabajo de parto" (Hofmeyer 2003). Esta revisión sólo incluye la comparación de prostaglandinas intracervicales con placebo y con prostaglandinas vaginales, excepto misoprostol (es decir, los métodos mencionados en una lista jerárquica de métodos para la inducción del trabajo de parto, ver sección "Métodos de la revisión").


OBJETIVOS

Determinar, a partir de la mejor evidencia disponible, la efectividad y seguridad de las prostaglandinas intracervicales para la maduración y la inducción del trabajo de parto durante el tercer trimestre con el placebo o ningún tratamiento y con las prostaglandinas vaginales (excepto el misoprostol). Un objetivo adicional consistió en comparar las dosis.


CRITERIOS PARA LA VALORACIÓN DE LOS ESTUDIOS DE ESTA REVISIÓN
Tipos de estudios

Ensayos clínicos que comparen la prostaglandina intracervical para la maduración cervical o la inducción del trabajo de parto con placebo o ningún tratamiento u otros métodos antes enumerados en una lista predefinida de métodos de inducción del trabajo de parto (para esta revisión, prostaglandinas vaginales, excepto misoprostol, ver "Métodos de la revisión"); los ensayos incluyeron alguna forma de asignación aleatoria para cada grupo; e informaron uno o más de los resultados especificados previamente.

Tipos de participantes

Mujeres embarazadas aptas para la inducción del trabajo de parto en el tercer trimestre, con un feto viable.

Los análisis de subgrupo preestablecidos son: presencia o ausencia de una cesárea previa; nuliparidad o multiparidad; membranas intactas o rotas, y cuello uterino desfavorable, favorable o indefinido. Solamente aparecen en las tablas de análisis aquellos resultados que contienen datos.

Tipos de intervención

(1) Prostaglandinas intracervicales comparadas con placebo o ningún tratamiento
(2) Prostaglandinas intracervicales comparadas con prostaglandinas vaginales (excepto misoprostol)
(3) Prostaglandinas intracervicales de dosis baja comparadas con dosis alta. La división entre regímenes de dosis baja y alta se realizó de la siguiente manera: por dosis baja se entiende cualquier régimen con una dosis de PGE2 intracervical inferior o igual a 0,5 mg e inferior o igual a dos dosis.

Tipos de medidas de resultado

Dos autores de revisiones sobre inducción del parto (Justus Hofmeyr y Zarko Alfirevic) han preestablecido aquellos resultados clínicamente relevantes en los ensayos sobre métodos de maduración cervical/inducción del parto. Las diferencias se resolvieron mediante consenso.

Se seleccionaron cinco medidas de resultado primarias como las más representativas de las medidas de importancia clínica de la efectividad y de las complicaciones.
(1) Parto vaginal no logrado al cabo de 24 horas;
(2) hiperestimulación uterina con cambios en la frecuencia cardíaca fetal (FCF);
(3) cesárea;
(4) morbilidad neonatal grave o mortalidad perinatal (p.ej., convulsiones, asfixia al nacer definida por los revisores, encefalopatía neonatal, discapacidad en la infancia);
(5) morbilidad o mortalidad materna grave (p.ej., rotura uterina, ingreso a la unidad de cuidados intensivos, septicemia).

La morbilidad y la mortalidad perinatal y materna son resultados compuestos. Ésta no es una solución ideal porque, evidentemente, algunos componentes son menos graves que otros. Es posible que una intervención cause más muertes pero menos morbilidad grave. Sin embargo, esto es poco probable en el contexto de la inducción del trabajo de parto en un embarazo a término. Todos estos eventos serán raros y será más fácil detectar un pequeño cambio en su incidencia si se presentan resultados compuestos. Se explorará la incidencia de los componentes individuales como medidas de resultado secundarias (ver más adelante).

Los resultados secundarios se relacionan con medidas de efectividad, complicaciones y satisfacción.

Medidas de efectividad
(6) Cuello uterino desfavorable o sin cambio después de 12 a 24 horas;
(7) aceleración oxitócica.

Complicaciones
(8) Hiperestimulación uterina sin cambios en la FCF;
(9) ruptura uterina;
(10) analgesia epidural;
(11) parto vaginal instrumental;
(12) líquido con meconio;
(13) Puntuación de Apgar menor a siete a los cinco minutos;
(14) ingreso a la unidad de cuidados intensivos neonatales;
(15) encefalopatía neonatal;
(16) muerte perinatal;
(17) discapacidad en la infancia;
(18) efectos secundarios maternos (p.ej., náuseas , vómitos, diarrea, fiebre alta);
(19) náuseas maternas;
(20) vómitos maternos;
(21) diarrea en la madre;
(22) otros efectos secundarios maternos;
(23) hemorragia postparto (según la definieron los autores del ensayo);
(24) complicaciones maternas graves (p.ej., ingreso a la unidad de cuidados intensivos, septicemia con exclusión de la rotura uterina);
(25) muerte de la madre.

Medidas de satisfacción
(26) Mujer no satisfecha;
(27) cuidador no satisfecho.

La "rotura uterina" incluyó todas las roturas de importancia clínica de los úteros sin cicatrizar o cicatrizados. Se excluyen las dehiscencias insignificantes de cicatrices observadas incidentalmente en el momento de la cirugía.

Si bien se buscaron todos los resultados mencionados, en las tablas solamente aparecerán los resultados de los análisis que poseen datos.

La terminología de hiperestimulación uterina es problemática (Curtis 1987). En las revisiones se utiliza el término "hiperestimulación uterina sin cambios en la FCF" para incluir la taquisistolia uterina (más de cinco contracciones en 10 minutos durante al menos 20 minutos) y la hipersistolia uterina o hipertonía (una contracción con una duración de al menos dos minutos) e "hiperestimulación uterina con cambios en la FCF" para referirse al síndrome de hiperestimulación uterina (taquisistolia o hipersistolia con cambios en la frecuencia cardíaca fetal, tales como desaceleraciones persistentes, taquicardia o variabilidad a corto plazo reducida).

Se incluyeron en el análisis los resultados que adoptaban medidas razonables para reducir el sesgo del observador; y si había datos disponibles para el análisis, según la asignación original.


ESTRATEGIA DE BÚSQUEDA PARA LA IDENTIFICACIÓN DE LOS ESTUDIOS
Ver: estrategia de búsqueda Cochrane Pregnancy and Childbirth Group

Se hicieron búsquedas en el Registro de Ensayos del Grupo Cochrane de Embarazo y Parto (Cochrane Pregnancy and Childbirth Group) mediante contacto con el Coordinador de Búsqueda de Ensayos (agosto 2007).

El Coordinador de Búsqueda de Ensayos (Trials Search Co-ordinator) mantiene el registro de ensayos del Grupo Cochrane de Embarazo y Parto (Cochrane Pregnancy and Childbirth Group) que contiene ensayos identificados de:
(1) búsquedas trimestrales en el Registro Cochrane Central de Ensayos Controlados (CENTRAL) (Cochrane Central Register of Controlled Trials - CENTRAL);
(2) búsquedas mensuales en MEDLINE;
(3) búsquedas manuales en 30 revistas y en los resúmenes de congresos importantes;
(4) búsqueda semanal de actualización permanente en otras 36 revistas, más alertas mensuales de correo electrónico en BioMed Central.

Los detalles de las estrategias de búsqueda para CENTRAL y MEDLINE, la lista de revistas y de resúmenes de congresos de la búsqueda manual y la lista de revistas revisadas mediante el servicio de actualización permanente se pueden encontrar en la sección "Estrategias de búsqueda para la identificación de estudios" dentro de la información editorial acerca del Grupo Cochrane de Embarazo y Parto (Cochrane Pregnancy and Childbirth Group).

A los ensayos identificados a través de las actividades de búsqueda descritas anteriormente se les asigna un código (o códigos) que depende del tema. Los códigos están ligados a los temas de revisión. El Coordinador de Búsqueda de Ensayos busca el registro de cada revisión mediante el uso de estos códigos en lugar de las palabras clave.

No se aplicó ninguna restricción de idioma.

La búsqueda inicial se realizó de forma simultánea para todas las revisiones de métodos de inducción del trabajo de parto, tal como se señala en el protocolo genérico para estas revisiones (Hofmeyr 2000).


MÉTODOS DE LA REVISIÓN

Se ha desarrollado una estrategia para manejar el gran volumen y complejidad de datos referentes a inducción del parto. Se estudiaron numerosos métodos y se examinaron los efectos que éstos tienen en varias categorías de mujeres sometidas a inducción del trabajo de parto. La mayoría de los ensayos se basa en intervenciones, que comparan dos o más métodos en diversas categorías de mujeres. Los clínicos y los padres necesitan que los datos estén organizados de acuerdo con las categorías de mujeres, para poder escoger cuál es el mejor método para un escenario clínico particular. Sería muy difícil extraer estos datos a partir de cientos de informes de ensayos en un solo paso. Por lo tanto, se desarró un método de extracción de datos en dos pasos. La extracción inicial de los datos se hace en una serie de revisiones primarias organizadas de acuerdo con los métodos de inducción del parto, siguiendo una metodología estandarizada. Posteriormente, los datos se extraerán a partir de revisiones primarias dentro de una serie de revisiones secundarias, organizados de acuerdo con las categorías de mujeres.

Para evitar la duplicación de los datos en las revisiones primarias, los métodos de inducción del trabajo de parto se han listado en un orden específico, de uno a 27. Cada revisión primaria incluye comparaciones entre uno de los métodos (de dos a 27) únicamente con los métodos que aparecen antes en la lista. De esta manera, la revisión sobre oxitocina intravenosa (4) incluirá solamente comparaciones contra prostaglandinas intracervicales (3), prostaglandinas vaginales (2) o placebo (1). Los métodos que se identifiquen en el futuro se agregarán al final de la lista. La lista actual es la siguiente:

(1) placebo/ningún tratamiento;
(2) prostaglandinas vaginales (Kelly 2003);
(3) prostaglandinas intracervicales (esta revisión);
(4) oxitocina intravenosa (Kelly 2001a);
(5) amniotomía (Bricker 2000);
(6) oxitocina intravenosa con amniotomía (Howarth 2001);
(7) misoprostol vaginal (Hofmeyr 2003);
(8) misoprostol oral (Alfirevic 2006);
(9) métodos mecánicos que incluyen el catéter extraamniótico de Foley (Boulvain 2001a);
(10) desgarro de bolsas (Boulvain 2005);
(11) prostaglandinas extraamnióticas (Hutton 2001);
(12) prostaglandinas intravenosas (Luckas 2000);
(13) prostaglandinas orales (French 2001);
(14) mifepristona (Neilson 2000);
(15) estrógenos con o sin amniotomía (Thomas 2001);
(16) corticosteroides (Kavanagh 2006a);
(17) relaxina (Kelly 2001c);
(18) hialuronidasa (Kavanagh 2006b);
(19) aceite de castor, baño o enema, o ambos (Kelly 2001b);
(20) acupuntura (Smith 2003);
(21) estimulación de la mama (Kavanagh 2005);
(22) coito (Kavanagh 2001b);
(23) métodos homeopáticos (Smith 2003);
(24) óxido nítrico (Kelly 2008);
(25) misoprostol oral o sublingual (Muzonzini 2004);
(26) hipnosis;
(27) otros métodos para la inducción del trabajo de parto.

Las revisiones principales se analizan según las siguientes categorías clínicas de las participantes:
(1) presencia o ausencia de una cesárea previa;
(2) nuliparidad o multiparidad;
(3) membranas intactas o rotas;
(4) cuello uterino favorable, desfavorable o indefinido.

Las revisiones secundarias incluirán todos los métodos de inducción del trabajo de parto para cada una de las categorías de mujeres para las que se han hecho análisis de subgrupos en las revisiones primarias. Por lo tanto, habrá seis revisiones secundarias de métodos de inducción del trabajo de parto en los siguientes grupos de mujeres:

(1) primíparas, con membranas intactas (cuello uterino desfavorable, favorable o indefinido);
(2) primíparas, con rotura de membranas (cuello uterino desfavorable, favorable o indefinido);
(3) multíparas, con membranas intactas (cuello uterino desfavorable, favorable o no definido);
(4) multíparas, con rotura de membranas (cuello uterino desfavorable, favorable o no definido);
(5) cesárea previa, con membranas intactas (cuello uterino desfavorable, favorable o no definido);
(6) cesárea previa, con rotura de membranas (cuello uterino desfavorable, favorable o no definido).

La intención del protocolo original fue incluir solamente a las cinco medidas de resultado primarias en las revisiones secundarias. Sin embargo, debido a la falta de datos sobre las medidas de resultado primarias, se modificó el protocolo para incluir las medidas de resultado secundarias en las revisiones secundarias.

Cada vez que se actualice una revisión primaria con datos nuevos, también se actualizarán las revisiones secundarias que incluyan datos que hayan cambiado.

Los ensayos incluidos en las revisiones primarias se obtuvieron a partir de un conjunto inicial de ensayos que comprendían todas las intervenciones utilizadas en la inducción del trabajo de parto (ver los detalles de la estrategia de búsqueda citados anteriormente). El proceso de obtención de datos se realizó centralizadamente. Fue inicialmente coordinado por la Clinical Effectiveness Support Unit (CESU) del Royal College of Obstetricians and Gynaecologists, UK, en colaboración con el Grupo de Embarazo y Parto de la Colaboración Cochrane (Cochrane Pregnancy and Childbirth Group). Sin embargo, debido al gran número de ensayos incluidos, dicho proceso fue completado por el Grupo Cochrane de Embarazo y Parto No fue posible realizar la doble extracción de datos para esta etapa final, y la extracción de datos fue realizada por uno de los miembros del Grupo de Embarazo y Parto mediante formularios de datos desarrollados centralmente.

Los ensayos se revisaron inicialmente en base a los criterios de elegibilidad, mediante un formulario estandarizado y los criterios de selección básicos que se especificaron anteriormente. A continuación, los datos se presentaron en un formulario estandarizado de extracción de datos, el cual se sometió a una prueba piloto para verificar su consistencia e integridad. En el proceso piloto participaron investigadores del CESU y revisores anteriores en el área de inducción del trabajo de parto.

Se obtuvo información relacionada con la calidad metodológica de los ensayos en diversos niveles. Este proceso se completó sin considerar los resultados del ensayo. La evaluación del sesgo de selección analiza de forma separada el proceso utilizado en la generación de la secuencia aleatoria y el método de encubrimiento de la asignación. Luego se clasificaron para el propósito de cada revisión como adecuados o inadecuados mediante el uso de los criterios que se describen en la Tabla 01.

Se evaluó el sesgo de ejecución con respecto a quién fue cegado en los ensayos, es decir, la participante, el cuidador, el evaluador de resultados o el analista. En muchos ensayos el cuidador, el evaluador y el analista eran la misma persona. Se buscaron detalles acerca de la factibilidad y la adecuación del cegamiento en todos los niveles.

Los análisis de subgrupo preestablecidos son: con o sin cesárea previa nuliparidad o multiparidad; membranas intactas o rotas; y cuello uterino desfavorable, favorable o indefinido. Solamente los resultados con datos aparecen en tablas de análisis.

Los datos de las medidas de resultado individuales fueron incluidos en el análisis si cumplían los criterios especificados anteriormente en "Tipos de medidas de resultado". Los datos de los ensayos incluidos se procesaron según se describe en el Manual Cochrane para las Revisiones Sistemáticas de Intervenciones (Cochrane Handbook for Systematic Reviews of Interventions) (Higgins 2006). Los datos extraídos de los ensayos se analizaron en base a la intención de tratar (cuando esto no se realizó en el informe original, se efectuó un nuevo análisis siempre que fuera posible). Si faltaban datos, se establecía contacto con los autores originales para obtener una aclaración. Si el desgaste fue tal que pudiera afectar significativamente los resultados, los datos se excluyeron del metanálisis. La responsabilidad de esta decisión, documentada con claridad, fue de los autores de las revisiones primarias. Una vez que los datos faltantes estén disponibles, se incluirán en los análisis.

Los datos se extrajeron de todos los ensayos elegibles para examinar cómo influyen los aspectos de calidad en el tamaño del efecto en un análisis de sensibilidad. En los ensayos con informes escasos, los aspectos metodológicos se informaron como inciertos o se buscó aclaración.

Debido al gran número de ensayos, no fue posible realizar una extracción de datos doble, de manera que el acuerdo entre las tres personas que obtuvieron los datos se evaluó en una muestra aleatoria de ensayos.

Una vez extraídos, los datos se distribuyeron entre revisores individuales para introducirlos en el programa informático Review Manager (RevMan 2003), se verificó su precisión, y se analizaron como ya se mencionó mediante RevMan 2003. Para los datos dicotómicos, se calcularon los riesgos relativos y los intervalos de confianza del 95% y, en ausencia de heterogeneidad, los resultados se combinaron mediante un modelo de efectos fijos.

Los criterios predefinidos para los análisis de sensibilidad incluyeron todos los aspectos de la evaluación de la calidad que se mencionan anteriormente, además de los sesgos de selección, ejecución y desgaste.

El análisis primario se limitó a los resultados preespecificados y al análisis de subgrupos. En el caso de hallar diferencias en resultados o subgrupos no especificados, éstos se analizarían post hoc, pero se identificarían claramente como tales para evitar el establecimiento de conclusiones injustificadas.


DESCRIPCIÓN DE LOS ESTUDIOS

Se incluyó en esta revisión un total de 56 ensayos (96 publicaciones).

Desde 1978 hasta la actualidad se ha realizado un gran número de estudios para evaluar la aplicación intracervical de PGE2 para madurar el cuello uterino e inducir el trabajo de parto. En general poseían un pequeño tamaño de la muestra (menos de 100 mujeres incluidas) y, por lo tanto, un poder estadístico limitado como para demostrar una diferencia de importancia clínica en los resultados. Entre los 28 ensayos incluidos que comparaban la PGE2 intracervical con placebo o ningún tratamiento (en total incluyeron 1956 y 1808 mujeres, respectivamente), nueve poseían un tamaño de la muestra total de más de 100 mujeres y, de éstos, cinco incluyeron a más de 200 mujeres en cada ensayo. Entre los 29 ensayos que compararon la PGE2 intracervical con la PGE2 intravaginal (en total incluyeron 1958 y 1923 mujeres, respectivamente), 13 poseían un tamaño de la muestra total de más de 100 mujeres y, de éstos, siete incluyeron a más de 200 mujeres en cada ensayo. Dos ensayos (Milliez 1993; Stiver 1991) que comparaban diferentes dosis de PGE2 (0,25 mg versus 0,5 mg y 0,2 mg versus 0,5 mg, respectivamente) incluyeron a 84 y 28 mujeres respectivamente.

Muchos estudios realizados en los ochenta fueron financiados por compañías que comercializaban análogos de la PGE2 (Upjohn, Kalamazoo), y algunos fueron informados por autores individuales (p.ej., ver los informes individuales de Noah 1987 y Trofatter 1993) así como los informes colectivos. A pesar del gran cuidado que se tuvo para evitar incluir datos duplicados, es posible que queden algunos, ya que los autores de estudios posteriores no siempre mencionan las publicaciones anteriores.

Otra de las dificultades en la realización de la revisión es que ciertos ensayos se publicaron exclusivamente como resúmenes con escasos datos disponibles (y pocas posibilidades de comunicación con los revisores para obtener aclaraciones). Además, los revisores utilizaron diversos protocolos de administración (p.ej., dosis inicial, frecuencia, número de dosis) de PGE2 intracervical. La dosis inicial habitual fue de 0,5 mg, aunque algunos revisores administraron 1 mg o más. La dosis inicial de PGE2 intracervical fue seguida, o no, de sucesivas administraciones a intervalos variables (desde cada tres horas hasta una vez por semana). La oxitocina, con o sin amniotomía, generalmente se administró después del procedimiento de maduración (es decir, cuando las condiciones del cuello uterino eran apropiadas) o luego de un período de tiempo preestablecido. Estos protocolos variables de administración de oxitocina pudieron haber influido en el resultado general de la inducción del trabajo de parto.

Ver tabla "Características de los estudios incluidos" para información detallada acerca de todos los ensayos incluidos y "Características de los estudios excluidos" para los detalles de los estudios excluidos".


CALIDAD METODOLÓGICA

La estrategia de búsqueda dio lugar a 158 referencias que se evaluaron para su inclusión. Se identificaron 109 estudios en estas referencias. De éstos, se incluyeron 56 ensayos (96 referencias). Se excluyeron 53 estudios (62 publicaciones).

Comparación de PGE2 intracervical con placebo o ningún tratamiento
Los 28 estudios incluidos informaron que las mujeres se asignaron al azar a la PGE2 intracervical, o a placebo, o a ningún tratamiento. La generación de la secuencia de asignación al azar se describió claramente en 11 estudios. En la mayoría de los ensayos que utilizaron placebo, la preparación del fármaco se realizó en la farmacia; de este modo se redujo el riesgo de inconvenientes en la generación de la secuencia. Cuando se utilizó placebo se consideró haberse logrado la ocultación de la asignación y el cegamiento de la paciente y el cuidador, debido a los escasos datos informados por los autores. Entre los seis ensayos con un brazo de control sin tratamiento, dos estudios informaron un método inadecuado de ocultación de la asignación (cuatro fueron inciertos). No se informó el cegamiento del evaluador de resultados. Nueve ensayos informaron el número de exclusiones o de pérdidas durante el seguimiento. Todos los ensayos que informaron al respecto poseían menos del 10% de exclusiones o pérdidas de participantes durante el seguimiento.

Comparación de PGE2 intracervical con PGE2 intravaginal
Los 29 estudios incluidos informaron que las pacientes se asignaron al azar a la PGE2 intracervical o intravaginal. La generación de la secuencia de asignación al azar se describió claramente en 12 estudios. Dieciséis ensayos informaron la ocultación de la asignación (por lo general mediante sobres cerrados opacos). Solamente tres estudios que utilizaron un procedimiento de doble simulación lograron el cegamiento de las pacientes y los cuidadores (tratamiento intracervical activo y placebo intravaginal versus placebo intracervical y tratamiento intravaginal activo). No se informó el cegamiento del evaluador de resultados. Doce ensayos informaron el número de exclusiones o de pérdidas durante el seguimiento. Once de éstos poseían menos del 10% de exclusiones o de pérdidas durante el seguimiento (el último excluyó 15 y 12 mujeres de las 208 del análisis).

Comparación de PGE2 intracervical de dosis baja versus dosis alta
Ambos ensayos informaron que las pacientes se asignaron al azar a diferentes dosis de PGE2. Uno de los estudios realizó la generación de la secuencia de asignación al azar con un sobre (Milliez 1993). Si embargo la ocultación de la asignación fue incierta debido a que los sobres no se describieron como opacos. No se hubo información acerca del cegamiento. No hubo pérdidas durante el seguimiento. El segundo ensayo, informado exclusivamente como resumen, no describió la secuencia de asignación al azar, ni la ocultación de la asignación, ni el cegamiento, ni el seguimiento (Stiver 1991).


RESULTADOS

Se incluyeron en esta revisión 56 ensayos con 7738 mujeres. Se hallaron datos para todas las medidas de resultado primarias.

Comparación de PGE2 intracervical con placebo o ningún tratamiento

Medidas de resultado primarias
Sólo cuatro estudios (Gilson 1993; Grünberger 1986; Ulmsten 1982; Ulmsten 1985), con 198 mujeres, informaron el número de mujeres que no logró el parto vaginal dentro de las 24 horas, con una disminución del riesgo con las PGE2 (riesgo relativo [RR] 0,61; intervalo de confianza [IC] del 95%: 0,47 a 0,79). El resultado informado por la mayoría, 27 ensayos con 3734 mujeres, fue la cesárea. Hubo una pequeña reducción, estadísticamente no significativa, en el riesgo de cesárea con el uso de PGE2 (RR 0,88; IC del 95%: 0,77 a 1,00). Este hallazgo fue estadísticamente significativo en un subgrupo de mujeres con membranas intactas y cuello uterino desfavorable (10 ensayos; RR 0,82; IC del 95%: 0,68 a 0,98). El riesgo de hiperestimulación con cambios en la frecuencia cardíaca fetal (FCF) no aumentó significativamente (12 ensayos con 2296 mujeres; RR 1,21; IC del 95%: 0,72 a 2,05). Sin embargo, el riesgo de hiperestimulación sin cambios en la FCF aumentó significativamente (11 ensayos con 2531 mujeres; RR 1,59; IC del 95%: 1,09 a 2,33). La mortalidad o morbilidad materna grave y la mortalidad o morbilidad neonatal grave fueron poco informadas y los hallazgos fueron similares en ambos grupos (RR 0,33; IC del 95%: 0,01 a 7,96 y RR 0,75; IC del 95%: 0,19 a 2,96; respectivamente).

Medidas de resultado secundarias
No se hallaron diferencias estadísticamente significativas en ninguna de las medidas de resultado secundarias informadas, excepto por los vómitos, con una aumento del riesgo con las PGE2 (cuatro ensayos, 1015 mujeres; RR 2,27; IC del 95%: 1,11 a 4,63). Ningún ensayo informó la rotura uterina, ni el uso de analgesia epidural, ni la encefalopatía neonatal, ni la discapacidad en la infancia, ni la insatisfacción de la paciente o del cuidador.

Comparación de PGE2 intracervical con PGE2 intravaginal

Medidas de resultado primarias
El número de mujeres que no logró el parto vaginal dentro de las 24 horas aumentó con la PGE2 intracervical (11 ensayos con 2200 mujeres; RR 1,26; IC del 95%: 1,12 a 1,41). No hubo modificaciones en el riesgo de cesárea (28 ensayos con 3781 mujeres; RR 1,07; IC del 95%: 0,93 a 1,22). El riesgo de hiperestimulación con cambios en la FCF (13 ensayos con 1428 mujeres; RR 0,76; IC del 95%: 0,39 a 1,49) y sin cambios en la FCF (13 ensayos con 1681 mujeres; RR 0,80; IC del 95%: 0,56 a 1,15) no fue significativamente diferente con ambos métodos de administración de PGE2. En pocas ocasiones se informó la morbilidad materna grave (RR 3,07; IC del 95%: 0,13 a 74,71). Solamente un ensayo informó un caso en el grupo de PGE2 intracervical (Irion 1998a), while two trials (Seeras 1995; Zanini 1989) informaron que no hubo muertes ni morbilidad grave.

Medidas de resultado secundarias
No hubo diferencias estadísticamente significativas en ninguna de las medidas de resultado secundarias informadas. Ningún ensayo informó acerca del cuello uterino desfavorable o sin cambios luego de 12 a 24 horas (como proporción), ni la encefalopatía neonatal, ni la discapacidad en la infancia, ni la mortalidad materna, ni la satisfacción de la paciente o del cuidador. Solamente un ensayo informó la opinión materna, con dos pacientes no satisfechas en el grupo intracervical (64 mujeres) versus tres en el grupo intravaginal (61 mujeres) (Lyndrup 1991).

Comparación de PGE2 intracervical de dosis baja versus dosis alta
El primer estudio, con 28 mujeres, comparó 0,2 mg con 0,5 mg de PGE2 intracervical en gel (Stiver 1991). Ambos grupos recibieron el gel a intervalos de seis horas hasta el momento del parto o de la rotura espontánea de membranas, de lo contrario se administró un máximo de cinco dosis. El ensayo sólo informó las tasas de cesárea y no hubo diferencias significativas entre los grupos (40% versus 30,8%; RR 1,30; IC del 95%: 0,47 a 3,62). El segundo estudio, con 84 mujeres, comparó 0,25 mg de PGE2 intracervical en gel administrado en forma diaria con 0,5 mg de PGE2 intracervical en gel administrado dos veces a intervalos de 12 horas (Milliez 1993). En el primer grupo se repitieron las aplicaciones hasta obtener una puntuación de Bishops mayor que 6, o bien hasta el deterioro del estado materno o fetal. El ensayo informó la hiperestimulación uterina con cambios en la FCF (14,2% versus 11,9%; RR 1,2; IC del 95%: 0,40 a 3,63) las tasas de cesárea (19% versus 31%; RR 0,62; IC del 95%: 0,28 a 1,33) y la utilización de estimulación ocitócica (28,6% versus 71,4%; RR 0,40; IC del 95%: 0,24 a 0,67).


DISCUSIÓN

En la actualidad, la vía de administración intracervical se utiliza menos y se la ha evaluado menos, y ha sido reemplazada ya sea por la administración vaginal de PGE2 o por el empleo de misoprostol. Uno de los motivos puede ser la dificultad para lograr una aplicación intracervical verdadera, pudiendo ocasionar pérdidas del producto desde el canal cervical hacia la vagina. Debido a que la dosis preenvasada es menor que la de la vía vaginal, esto podría explicar la menor eficacia de las prostaglandinas intracervicales comparadas con las vaginales. Es sorprendente que esté disponible tan poca información relativa a esta cuestión en los ensayos incluidos. Del mismo modo, un solo revisor evaluó la opinión materna sobre la atención recibida, y no hubo datos acerca de la satisfacción del cuidador.

Prostaglandinas intracervicales versus placebo o ningún tratamiento
El empleo de prostaglandinas intracervicales parece ser más efectivo que el placebo o ningún tratamiento, especialmente en mujeres con cuello uterino desfavorable o con membranas intactas. Sin embargo, la única medida de resultado informada por la mayoría de los revisores fue la cesárea; hubo menos datos sobre los demás resultados. Muchos de los informes sólo se publicaron como resúmenes con un número escaso de detalles y de datos. Tampoco quedó claro, en determinados estudios, si las participantes también habían sido incluidas en un ensayo multicéntrico amplio (ver "Descripción de los estudios"). Se excluyeron todos los estudios que se sospechó que podrían integrar el ensayo multicéntrico, para minimizar la posibilidad de duplicación de datos. Los resultados de ciertas medidas de resultado (p.ej., no lograr el parto vaginal dentro de las 24 horas) revelan heterogeneidad, pero el uso de un modelo de efectos aleatorios no produce cambios considerables en la estimación del efecto proporcionada por el modelo de efectos fijos.

Prostaglandinas intracervicales versus prostaglandinas intravaginales
Se demostró que las prostaglandinas intracervicales son menos efectivas que la prostaglandina intravaginal. Dicha conclusión está limitada por el hecho de que existe heterogeneidad significativa entre los ensayos para la comparación del número de mujeres que "no logró el parto vaginal dentro de las 24 horas". La vía intravaginal debería resultar más fácil y menos incómoda para la paciente. Es sorprendente que ningún ensayo, excepto uno, informe sobre esta cuestión. Aparentemente, esta situación, sumada a una eficacia percibida similar o inferior, ha sido el motivo por el cual muchos centros abandonaron dicha vía de administración.

PGE2 intracervical de dosis baja versus PGE2 intracervical de dosis alta
En general los datos de los tres ensayos fueron insuficientes como para establecer comparaciones significativas entre las dosis.


CONCLUSIONES DE LOS AUTORES
Implicaciones para la práctica

Las prostaglandinas intracervicales son efectivas pero no poseen ventajas con respecto a la prostaglandina intravaginal. Por lo tanto, en caso de indicarse la administración de prostaglandinas, se debe preferir la vía intravaginal, ya que es más efectiva y más práctica.

Implicaciones para la investigación

A pesar de las limitaciones de las pruebas disponibles, es poco factible que se investigue más acerca del uso de las PGE2 intracervicales. También sería importante evaluar la seguridad y los beneficios del uso de las prostaglandinas E2 (posiblemente por vía vaginal) en mujeres con antecedentes de cesárea, ya que hay pocos datos provenientes de ensayos aleatorios al respecto.


AGRADECIMIENTOS

R. Smyth (mientras trabajaba como Asistente Editorial en la base editorial del Grupo Cochrane de Embarazo y Parto) colaboró con las siguientes secciones: Secciones: Resumen, Descripción de los estudios, Calidad metodológica de los estudios incluidos y Resultados R. Smyth evaluó parte de los estudios para su inclusión, extrajo e ingresó los datos de forma independiente.

Lixia Dou, por haber completado la tabla "Características de los estudios incluidos" de numerosos estudios.

Se dan especialmente las gracias a Ingemar Ingemarsson (Ingemarsson 1991); Mike Lucas y Alex Vidaeff (Trofatter 1993); Charles Nager (Nager 1987); y Mike Wyldes (Wyldes 1992) quien tuvo la amabilidad de proporcionar información no publicada para esta revisión.

Como parte del proceso editorial previo a la publicación, se han realizado observaciones sobre esta revisión por tres pares (un editor y dos consultores externos al equipo editorial), uno o más miembros del panel internacional de consumidores del Grupo de Embarazo y Parto y el Asesor Estadístico del Grupo.


POTENCIAL CONFLICTO DE INTERÉS

Ninguno conocido.


TABLAS

Characteristics of included studies

StudyBernstein 1991 
MethodsRandomisation: RCT. Method of generation of the allocation sequence unclear.
Allocation concealment: concealment of the allocation by opening drug boxes. Prepackaged preparations were used that had been coded by the pharmacy.
Blinding: 'double-blind'.
Follow up: 17 exclusion, but ITT analysis possible. 
Participants397 women were enrolled, 203 in experimental group and 194 in control group.
Eligibility: gestational age of at least 36 weeks, parity of 3 or less, a Bishop score of 4 or less, intact membranes and a medical or obstetric indication for induction, as decided by the attending physician.
Exclusion: any contraindication to vaginal delivery, a history of CS or major uterine surgery, a known hypersensitivity to prostaglandins, any previous attempt at cervical ripening or induction, suspected or clinically evident fetal compromise, vaginal bleeding, rupture membranes or fetal death in utero.
On admission to hospital the women were observed for 30 minutes before gel insertion. During this time their vital signs were recorded, the FHR and uterine activity were assessed with the use of a nonstress test, and the initial laboratory test (complete blood count, renal and liver function test and urinanalysis) were performed. Evidence of any abnormalities or labour was sufficient for exclusion from the study. 
InterventionsExperimental: IC gel PGE2 0.5 mg 1 dose.
Control group: IC placebo gel 1 dose.
If labour begun women were managed and monitored by the attending physician as deemed appropriate. Amniotomy was not performed until the cervix had dilated to 3 cm or more. Under no circumstances were any other uterotonic drugs such as oxytocin administered until at least 6 hours after the gel had been inserted unless delivery had occurred. Women not in labour in 12 hours after the administration were induced with oxytocin according to the induction protocol in each institution. Unless contraindicated by a particular medical problem (fetal or maternal), induction with oxytocin was continued either until labour started or for a maximum of 12 hours. Management of women who could not be induced and of labour was left to the discretion of the attending physician. 
OutcomesWomen: uterine hyperstimulation with FHR changes, CS., uterine hyperstimulation without FHR changes.
Fetal/infant: no outcomes reported. 
NotesMulticentre/single centre: multi-centre.
Setting: Canada.
Additional outcomes reported: Bishop score at 12 hours after gel treatment, spontaneous labour, interval from gel administration to delivery, uterine hypercontractility, Apgar score at 1 and 5 minutes, neonatal jaundice, FHR abnormalities. 
Allocation concealmentA - Adequate 
StudyButtino 1990 
MethodsRandomisation: RCT. Randomisation was generated in the pharmacy.
Allocation concealment: sequentially-numbered syringes which were visual identical.
Blinding: 'double blind' study.
Follow up: no loss of participants reported. 
Participants43 women were enrolled , 23 in experimental group and 20 in control group.
Eligibility: with a pregnancy of at least 41 weeks and 6 days of gestation; free of any contraindications to the use of prostaglandins.
Exclusion: no information provided. 
InterventionsExperimental: IC gel PGE2 0.5 mg.
Control: IC placebo gel. 
OutcomesWomen: vaginal delivery not achieved within 24 hours, uterine hyperstimulation with FHR change, CS.
Fetal/infant: no outcomes reported. 
NotesMulticentre/single centre: single centre.
Setting: USA.
Additional outcomes reported: change in Bishop score, spontaneous labour, length of labour, interval from dosage to delivery, delivery within 72 hours, Apgar score at 1 minute, Apgar score at 5 minutes, birthweight. 
Allocation concealmentA - Adequate 
StudyCabrol 1988 
MethodsRandomisation: RCT. Method of generation of the allocation sequence unclear.
Allocation concealment: unclear.
Blinding: 'double blind'.
Follow up: no loss of participants reported. 
Participants208 women were enrolled, 104 in experimental group and 104 in control group.
Eligibility: pregnancy at term, unripe cervix, a medical indication for induction.
Exclusion: no information provided. 
InterventionsExperimental group: IC gel PGE2 0.5 mg (1 dose).
Control group: IC placebo gel (1 dose). 
OutcomesWomen: hyperstimulation, CS, PPH, diarrhoea.
Fetal/infant: Apgar score. 
NotesMulticentre/single centre: single centre.
Setting: France.
Additional outcomes reported: delivery within 12 hours.
The paper was written in French and needed to be translated. 
Allocation concealmentB - Unclear 
StudyChyu 1997 
MethodsRandomisation: RCT, computer-generated random numbers.
Allocation concealment: unclear.
Blinding: unclear.
Follow up: 12 women were excluded because of violation of study protocol, 7 from the gel group and 5 from pessary group. No participants withdrew from the study. 
Participants85 women were enrolled, 43 in the gel group and 42 in the pessary group.
Eligibility: (1) Bishop score no more than 7, (2) cervical dilatation of < 4 cm, (3) no more than 2 cm of dilatation if effacement exceeded 70%, (4) reassuring fetal wellbeing, defined as the present of either a reactive nonstress test or a biophysical profile score > 8 (of 10).
Exclusion: (1) results of cervical examination not meeting the criteria for inclusion, (2) suspicion or evidence of fetal distress, defined as biophysical profile score < 8 (of 10) or the presence of late or severe variable decelerations, (3) current vaginal bleeding, (4) more than 6 previous term pregnancies, (5) presence of a contraindication to oxytocic drugs, (6) fever of undetermined cause, (7) active and severe asthma, (8) allergy to prostaglandins, or (9) chorioamnionitis. 
InterventionsGel group: 0.5 mg dinoprostone for IC application. At 6-hour intervals the cervix was re-examined, and if the cervix continued to meet the inclusion criteria, the dose was repeated up to a maximum of 3 total doses.
Pessary group: 10 mg intravaginal controlled-release dinoprostone pessary, single dose. The pessary was removed after 12 hours; it was to be removed earlier only with the onset of active labour or with the occurrence of uterine hyperstimulation accompanied by an abnormal fetal heart tracing.
If active labour had not already begun, oxytocin infusion was initiated 6 hours after the final dose of gel was administered or 30 minutes after the pessary was removed. Amniotomy was performed at the discretion of the attending physician. Oxytocin induction was to be continued for a minimum of 14 hours unless contraindications arose. 
OutcomesWomen: CS , instrumental vaginal delivery, uterine hyperstimulation with FHR changes, uterine hyperstimulation without FHR changes, diarrhoea, postpartum haemorrhage.
Fetal/infant: Apgar score < 7 at 5 minutes. 
NotesMulticentre/single centre: single centre.
Setting: USA.
Additional outcomes reported: change of Bishop score, time to active labour, ripening time, latent labour, length of active labour, length of second stage of labour, time to vaginal labour, hospital stay, vaginal delivery, treatment failure, fever, birthweight, arterial and venous cord pH < 7.2. 
Allocation concealmentB - Unclear 
StudyCorrado 2001 
MethodsRandomisation: RCT. Randomisation generated by computer.
Allocation concealment: women were randomly assigned by computer.
Blinding: unclear.
Follow up: no loss of participants reported. 
Participants233 women were enrolled, 122 in the IC group and 111 in the intravaginal group.
Eligibility: evaluated for labour induction, absence of spontaneous labour, intact membranes, a Bishop score no more than 5, with gestational age at least 34 weeks and reactive nonstress test.
Exclusion: twin pregnancies, previous CS, previous uterine surgery or breech presenting fetus. 
InterventionsExperimental: IC gel dinoprostone 0.5 mg.
Control: intravaginal gel dinoprostone 1 mg.
An intravaginal dose of 2 mg of dinoprostone gel was applied after 4 hours, if the Bishop score was still <6, and repeated 4 hours later. Sometimes, oxytocin was given for the augmentation of labour when the Bishop score became favourable. 
OutcomesWomen: CS, oxytocin augmentation, instrumental vaginal delivery.
Fetal/infant: no outcomes reported. 
NotesMulticentre/single centre: single centre.
Setting: Italy.
Additional outcomes reported: spontaneous delivery, spontaneous delivery within 24 hours, time from treatment to vaginal delivery, birthweight, Apgar score at 1 minute, Apgar score at 5 minutes, uterine hyperstimulation, hypersensitivity to prostaglandin gel. 
Allocation concealmentA - Adequate 
StudyDarroca 1996 
MethodsRandomisation: RCT. Computer-generated allocation sequence.
Allocation concealment: using centrally-prepared syringes.
Blinding: 'double blind'.
Follow up: no loss of participants reported. 
Participants118 women were enrolled, 61 in experimental group and 57 in control group.
Eligibility: confirmed indications for induction of labour, with a gestational age before 41 completed weeks.
Exclusion: a scarred uterus, history of hypersensitivity to PGE2 or the base used to carry the medication, a Bishop score of 6 or more. 
InterventionsExperimental: IC gel PGE2 0.5 mg.
Control: IC placebo gel.
If the NST or CTS was reassuring, the participant was given the first dose of gel and monitored for an additional hour. If the post-dose NST or CST was reassuring, the participant was sent home. In either case, the participant was re-examined in 14-16 hours and another Bishop score was assigned. If the Bishop score was still less than 6, the participant was given another dose of the same gel and oxytocin induction was begun immediately; if the Bishop score was at least 6, oxytocin induction was begun without a second dose of gel. Amniotomy was accomplished as early as possible. 
OutcomesWomen: CS.
Fetal/infant: no outcomes reported. 
NotesMulticentre/single centre: single centre.
Setting: USA.
Additional outcomes reported: a more than 2-point change in Bishop score, interval from insertion of the gel to complete dilation, Apgar score < 9 at 1 minute, Apgar score < 9 at 5 minute, mean umbilical artery pH. 
Allocation concealmentA - Adequate 
StudyDuhl 1997 
MethodsRandomisation: RCT. Method of generation of the allocation sequence unclear.
Allocation concealment: unclear.
Blinding: unclear.
Follow up: no loss of participants reported. 
Participants74 women were enrolled, 24 in intravaginal gel group, 27 in intravaginal time release group and 23 in IC gel group.
Eligibility: a medical indication for inpatient induction of labour.
Exclusion: no information provided. 
InterventionsIntravaginal gel group: intravaginal gel PGE2 3 mg, every 4 to 6 hours until intravenous oxytocin was started.
Intravaginal time release group: 10 mg time release intravaginal insert with dinoprostone, every 12 hours until intravenous oxytocin was started.
IC gel group: IC gel dinoprostone 0.5 mg, every 6 hours until intravenous oxytocin was started. 
OutcomesWomen: no outcomes reported.
Fetal/infant: no outcomes reported. 
NotesMulticentre/single centre: single centre.
Setting: USA.
Additional outcomes reported: change in Bishop score, labour initiation, uterine hyperstimulation.
Abstract only. 
Allocation concealmentB - Unclear 
StudyEkman 1983 
MethodsRandomisation: random allocation stratified for parity. No other details reported.
Allocation concealment: unclear.
Blinding: unclear.
Follow up: no loss of participants reported. 
Participants60 women were enrolled, 30 (15 nulliparous women and 15 multiparous women) were in IC application group and 30 (15 nulliparous women and 15 multiparous women) in intravaginal application group.
Eligibility: term women with an unripe cervix, intact membranes, vertex presentation, no uterine contraction and obstetric indications for induction.
Exclusion: placenta previa and multiple pregnancy. 
InterventionsIC application group: IC PGE2 0.5 mg in 2 ml of gel.
Intravaginal application group: Intravaginal PGE2 4 mg in 3 ml of gel.
In all participants in whom labour was not induced but in whom a favourable cervical state (cervical score > 5) was registered 5 hours after application of gel, intravenous infusion of oxytocin was instituted. Amniotomy was not undertaken until labour was well established and the cervix was dilated to at least 4 cm. 
OutcomesWomen: vomiting, CS.
Fetal/infant: Apgar score < 7 at 5 minute. 
NotesMulticentre/single centre: single centre.
Setting: Sweden.
Additional outcomes reported: favourable cervical state after 5 hours, favourable cervical state after 5 hours (women with highly unfavourable cervix), delivery within 12 hours, intrauterine pressure, painful uterine contraction, bleeding, rupturing of membranes. 
Allocation concealmentB - Unclear 
StudyEl-Din 2000 
MethodsRandomisation: RCT, method of generation of the allocation sequence unclear.
Allocation concealment: unclear.
Blinding: unclear.
Follow up: no loss of participants reported. 
Participants149 women were enrolled, 52 in the misoprostol group, 49 in the tablet PGE2 group and 48 in the prepidil group.
Eligibility: women with unfavourable cervix.
Exclusion: no information provided. 
InterventionsMisoprostol group: intravaginal misoprostol 50 µg every 4 hours for 24 hours or until adequate labour was achieved.
Tablet PGE2 group: intravaginal tablet PGE2 3 mg every 4 hours for 24 hours or until adequate labour was achieved.
Prepidil group: IC prepidil gel (PGE2 gel) every 6 hours (maximum 3 doses) for 24 hours or until adequate labour was achieved. 
OutcomesWomen: CS.
Fetal/infant: no outcomes reported. 
NotesMulticentre/single centre: single centre.
Setting: Egypt.
Additional outcomes reported: interval from treatment to delivery, tachysystole and hyperstimulation, abnormal FHR trace.
Abstract only. 
Allocation concealmentB - Unclear 
StudyGilson 1993 
MethodsRandomisation: RCT. No details of generation of randomisation.
Allocation concealment: the assignment was blinded to both physician and participant, the randomisation having been carried out in pharmacy.
Blinding: 'double blind'.
Follow up: no loss of participants reported. 
Participants79 women were enrolled, 41 in experimental group and 38 in control group.
Eligibility: admitted for the induction of labour, single pregnancy, intact membranes, no evidence of fetal compromise, with a Bishop score of 4 or less.
Exclusion: with a history of asthma, glaucoma, ruptured membranes, breech presentation, abnormal vaginal bleeding, or with 2 or more CS. 
InterventionsExperimental: IC gel dinoprostone 0.5 mg.
Control: IC placebo gel.
12 hours after the gel had been placed, oxytocin induction was begun. Amniotomy was done when the participant was in active labour and cervical dilatation allowed it. If the maternal and fetal surveillance was reassuring, the participant was rested overnight and oxytocin was readministered the following day. The oxytocin infusion rate was not allowed to exceed 20 milliunits per minute. 
OutcomesWomen: vaginal delivery not achieved within 24 hours, CS.
Fetal/infant: no outcomes reported. 
NotesMulticentre/single centre: single centre.
Setting: USA.
Additional outcomes reported: 12-hour Bishop score, change in Bishop score, gel-instillation interval, oxytocin-administration time, spontaneous labour after gel, hyperstimulation, fetal distress, infant weight, Apgar score at 5 minutes. 
Allocation concealmentA - Adequate 
StudyGrünberger 1986 
MethodsRandomisation: 'prospective randomised study' .
Allocation concealment: no information provided.
Blinding: no information provided.
Follow up: no loss of participants up to 24 hours after randomisation. 
Participants30 women were enrolled, 15 in experimental group and 15 in control group.
Eligibility: 41-42 weeks' gestation, unfavourable cervix.
Exclusion: maternal or fetal risk factors, twin pregnancies, breech presentation, previous CS, previous operations on the uterine cervix. 
InterventionsExperimental: 1.5 mg PGE2 instilled into cervical cap.
Control: 3 ml 0.9% saline instilled into cervical cap.
For all women 6 hours later if contractions regular cervical cap was removed, if no contractions each group received a repeat of intervention for 6 hours. If after 24 hours labour not commenced a 'cross-over' was made to the respective alternative group on the morning of the second day. 
OutcomesMaternal: not delivered within 24 hours.
Fetal/infant: no outcomes reported. 
NotesMulticentre/single centre: single-centre.
Setting: Austria.
Additional outcomes:maternal serum 13, 14- Dihydro-15-Keto-PGF and progesterone.
A number of attempts made to contact author and co-author to verify if all deliveries were vaginal. Attempts were unsuccessful - April 2007. 
Allocation concealmentB - Unclear 
StudyHales 1994 
MethodsRandomisation: RCT. Computer-generated randomisation schedule.
Allocation concealment: syringes were sent from the pharmacy to the labour and delivery unit for each enrolled participant .
Blinding: 'double blind'.
Follow up: 8 were excluded, 2 for unsuspected ruptured membranes and 6 for failure to properly follow the redosing protocol. 
Participants108 women were enrolled, 52 in IC gel group, 48 in intravaginal group and 8 excluded.
Eligibility: all inpatients deemed to have a medical indication for induction of labour in spite of an unfavourable cervix (BS equal to or less than 4). Each had undergone electronic FHR monitoring, and a reactive nonstress test result had to be present.
Exclusion: vaginal bleeding, ruptured membranes, noncephalic fetal presentation, history of asthma, or uterine contractions more frequently than every 8 minutes. 
InterventionsIC gel group: IC gel PGE2 0.5 mg + intravaginal placebo gel.
Intravaginal gel group: intravaginal gel PGE2 j2.5 mg + IC placebo gel.
Each enrollee was administered simultaneous doses of an IC, then an intravaginal, preparation of the gel. 1 preparation contained PGE2, whereas the other was placebo (methylcellulose only).
Each participant was re-examined 6 hours after dosing. Those whose cervix remained unfavourable without labour were given a second and third pair of the same batch of syringes. If the cervix favourable (Bishop score > 6), an early amniotomy was performed if the fetal head was applied to the cervix, and oxytocin infusion was instituted if necessary. If no cervical change (Bishop score change no more than 3 from original predosing) or regular contractions occurred after the third dose, oxytocin was infused for induction of labour. 
OutcomesWomen: vaginal delivery not achieved in 24 hours, CS, vomiting, diarrhea, oxytocin augmentation.
Fetal/infant: Apgar score < 7 at 5 minutes. 
NotesMulticentre/single centre: single centre.
Setting: USA.
Additional outcomes reported: oxytocin need (for induce), instillation to vaginal delivery (hour), vaginal delivery within 36 hours, vaginal delivery within 48 hours, CS (for failed induction), CS (for failure to progress), CS (for suspected fetal distress), Bishop score change > 3, regular contractions, active labour, maternal temperature > 100 F, hyperstimulation, abnormal FHR pattern, infant sex, birthweight (< 2500 gm), birthweight (> 4000 gm), Apgar score < 7 at 1 minute.
Note: the gel was noted to spill out of the cervix during IC application in the majority (85.0%). 
Allocation concealmentA - Adequate 
StudyHeinzl 1980 
MethodsRandomisation: RCT, method of generation of the allocation sequence unclear.
Allocation concealment: unclear.
Blinding: 'double blind'.
Follow up: 4 participants were dropped for documentation errors. 
Participants124 women were enrolled, 60 in experimental group, 60 in control group and 4 dropped.
Eligibility: singleton, > 36 gestational weeks, Bishop score less than 6, vertex.
Exclusion: previous LSCS, other uterine scar. 
InterventionsExperimental: IC gel PGF2a 5 mg.
Control: placebo. 
OutcomesWomen: CS, uterine hyperstimulation without FHR changes, instrumental vaginal delivery, nausea, vomiting.
Fetal/infant: no outcomes reported. 
NotesMulticentre/Single centre: single centre.
Setting: Switzerland.
Additional outcomes reported: birth within 36 hours.
This paper was written in German and needed to be translated. 
Allocation concealmentB - Unclear 
StudyHidar 2000 
MethodsRandomisation: RCT. Computer-generated sequence.
Allocation concealment: unclear.
Blinding: none.
Follow up: all women. 
Participants88 women were enrolled, 44 in experimental group and 44 in control group.
Eligibility: term, singleton, live fetus, unfavourable cervix (BS < 5), ruptured membranes, no previous uterine scar.
Exclusion: previous uterine scar, fever, urgent delivery. 
InterventionsExperiment: IC gel PGE2 0.5 mg (1 dose), followed by oxytocin administration.
Control: conservative management for up to 24 hours.
24 hours after, oxytocin administration. 
OutcomesWomen: CS, oxytocin augmentation, instrumental vaginal delivery, vomiting, postpartum haemorrhage.
Fetal/infant: perinatal death. 
NotesMulticentre/single centre: single centre.
Setting: France.
Additional outcomes reported: intervals form PROM to delivery, interval from inclusion to start of labour, duration of labour, amnionitis, mode of delivery, Apgar score, uterine tachysystole.
This paper was written in French and needed to be translated. 
Allocation concealmentB - Unclear 
StudyHutchon 1980 
MethodsRandomisation: RCT, no details of generation of randomisation.
Allocation concealment: by a set of vials identified by number only.
Blinding: 'double blind'.
Follow up: no loss of participants reported. 
Participants67 women were enrolled, 32 in experimental group and 35 in control group.
Eligibility: a modified Bishop score of 4 or less, singleton pregnancy, cephalic presentation, normally sited placenta, no history of antepartum haemorrhage, an unscarred uterus, no previous cervical surgery, an obstetric indication for induction.
Exclusion: no information provided. 
InterventionsExperimental: IC gel PGE2, 450 µg for the initial 14 participants and 650 µg for the subsequent 18 participant .
Control: IC placebo gel.
All participant were requested to remain in bed for 2 hours and amniotomy was carried out on the morning of induction. 
OutcomesWomen: CS, meconium stained liquor.
Fetal/infant: serious neonatal morbidity or perinatal death. 
NotesMulticentre/single centre: single centre.
Setting: UK.
Additional outcomes reported: established labour or delivery before planned induction, induction delivery interval, length of labour, fetal distress, improvement of cervical score. 
Allocation concealmentA - Adequate 
StudyIrion 1998 
MethodsRandomisation: RCT. Computer-generated allocation sequence.
Allocation concealment: by central randomisation.
Blinding: unclear.
Follow up: no women excluded. 
Participants247 women were enrolled, 122 in the IC group and 125 in the vaginal group.
Eligibility: gestational age greater than 30 completed weeks, singleton, cephalic presentation, Bishop score 4 or less, intact membranes, absence of spontaneous labour, and reassuring electronic fetal monitoring.
Exclusion: asthma. 
InterventionsIC group: lC gel PGE2 0.5 mg.
Vaginal group: intravaginal gel PGE2 2 mg.
If the Bishop score was 4 or less, another dose of PGE2 was given after 6 hours, and up to 2 additional doses were given 6 hours apart on the second day. An oxytocin infusion was begun when the Bishop score was 5 or greater in absence of spontaneous labour, or if labour had not begun on the third day. 
OutcomesWomen: CS, serious maternal morbidity or death, oxytocin augmentation, uterine rupture, epidural analgesia, instrumental delivery, maternal side-effects (nausea, vomiting, diarrhoea and fever).
Fetal/infant: Apgar score < 7 at 5 minutes. 
NotesMulticentre/single centre: single centre.
Setting: Switzerland.
Additional outcomes reported: cervical ripening, time to cervical ripening, interval from treatment to vaginal delivery, time from gel application to the onset of cervical dilatation, time from the onset of cervical dilatation to full dilatation, oxytocin induction, vaginal discomfort, arterial cord pH, maternal hemoglobin loss, length of maternal hospital stay, length of neonatal hospital stay, uterine hyperstimulation.
Also reported as abstract (Pedrazzoli et al.) 
Allocation concealmentA - Adequate 
StudyKeirse 1995 
MethodsRandomisation: RCT, method of generation of the allocation sequence unclear.
Allocation concealment: by numbered, opaque, sealed envelopes stratified for parity (nulliparous, parous) and Bishop score (no more than 5, > 5).
Blinding: unclear.
Follow up: 3 women were excluded after trial entry. 
Participants285 women were enrolled, 143 in cervical group, 141 in vaginal group and 1 whose case record was lost.
Eligibility: a singleton pregnancy of at least 37 weeks with a live fetus in vertex position and a medical or obstetric reason to justify induction of labour.
Exclusion: a previous CS or an earlier induction attempt in the current pregnancy. 
InterventionsCervical group: endocervical PGE2 0.5 mg in triacetin gel was inserted in the cervical canal.
Vaginal group: vaginal PGE2 was introduced in the posterior vaginal fornix.
If after 6 hours the membranes were still intact and the women were not in progressive labour, a further dose of prostaglandin, 0.5 mg endocervically or 1.0 vaginally, was administered. This could be repeated after a further 6 hours if necessary and if the membranes were still intact and the clinicians were free to use either 1.0 or 2.0 mg of PGE2 for women in the vaginal group. 
OutcomesWomen: vaginal delivery not achieved in 24 hours, uterine hyperstimulation with FHR changes, CS, oxytocin augment, uterine hyperstimulation without FHR changes, instrumental vaginal delivery, meconium stained liquor, PPH.
Fetal/infant: Apgar score < 7 at 5 minutes, NICU admission. 
NotesMulticentre/single centre: multi-centre.
Supported by an educational grant from Upjohn Co., Kalamazoo.
Setting: Netherlands.
Additional outcomes reported: not delivered (within 12 hours, 24 hours or 36 hours), operative delivery, no vaginal delivery < 26 hours, use of tocolytic agent, manual removal of placenta, postpartum bleeding (> 500 ml or > 1000 ml), blood transfusion, fever, Apgar score < 7 at 1 minute, resuscitation at birth, meconium aspiration, not discharged with mother. 
Allocation concealmentA - Adequate 
StudyKemp 2000 
MethodsRandomisation: RCT, using a stratified block randomisation.
Allocation concealment: unclear.
Blinding: unclear.
Follow up: no loss of participants reported. 
Participants470 women were enrolled, 241 in IC group and 229 in vaginal group.
Eligibility: a Bishop score of 3 and 4, singleton pregnancy with vertex presentation and a medical reason for induction of labour.
Exclusion: contraindications for prostaglandins, previous uterine surgery with incision of the uterine cavity, previous caesarean delivery by longitudinal section, marked uterine anomaly, abnormal FHR (Fischer score < 7), multiple gestation or nonvertex presentation. 
InterventionsIC group: IC gel PGE2 0.5 mg.
Vaginal group: intravaginal gel PGE2 2 mg.
The prostaglandin preparation was administered sequentially every 6-8 hours up to 3 times daily until the cervix became favourable (Bishop score > 7). Following 3 unsuccessful applications, the participant had 24 hours of rest before proceeding according to the clinical situation. In participants with a Bishop score > 7 oxytocin was administered 8 hours after the last PGE2 application. 
OutcomesWomen: vaginal delivery not achieved in 24 hours, CS, oxytocin augmentation, maternal side-effects.
Fetal/infant: Apgar score < 7 at 5 minutes. 
NotesMulticentre/single centre: multi-centre.
Setting: Germany.
Additional outcomes reported: changes in Bishop scores, induction-delivery interval, uterine hyperstimulation, prolonged uterine contractions, tocolytic treatment, umbilical artery pH < 7.20. 
Allocation concealmentB - Unclear 
StudyLarmon 2002 
MethodsRandomisation: RCT. Sequence prepared with a table of random numbers.
Allocation concealment: opaque, numbered and sealed envelopes.
Blinding: unclear.
Follow up: 8 women were excluded after randomisation. 
Participants84 women were enrolled, 41 in experimental group and 43 in control group.
Eligibility: women at term, unfavourable cervix (BS < 7), no pregnancy complications.
Exclusion: no information provided. 
InterventionsExperimental: IC PGE2 gel 0.5 mg weekly.
Control: IC placebo gel weekly.
Participants were instructed to proceed to the labour and delivery suite if membranes ruptured, regular uterine contractions began, or vaginal bleeding occurred. 
OutcomesWomen: CS, instrumental vaginal delivery, oxytocin augmentation, meconium stained liquor.
Fetal/infant: NICU admission. 
NotesMulticentre/single centre: single centre.
Setting: USA.
Additional outcomes reported: spontaneous vaginal delivery, Bishop score and change in Bishop score (admission), days to admission, maternal complications (endomyometritis, chorioamnionitis, septic pelvic vein thrombophlebitis, pre-eclampsia), birth weight, Apgar score at 1 minute, Apgar score at 5 minute, arterial cord blood pH, transient tachypnea of the newborn, meconium aspiration. 
Allocation concealmentA - Adequate 
StudyLaube 1986 
MethodsRandomisation: RCT. Randomisation had been accomplished before the study. No details of generation of randomisation.
Allocation concealment: numbered syringes sequentially released by the hospital pharmacy.
Blinding: 'double blind'.
Follow up: no loss of participants reported. 
Participants45 women were enrolled, 15 in each group.
Eligibility: unfavourable cervixes as indicated by Bishop scores of 4 or less, singleton pregnancies and cephalic presentations, reactive nonstress tests, afebrile, medical or obstetric complications justifying induction of labour, of parity 0 to 3.
Exclusion: previous uterine scar, vaginal bleeding, premature rupture of membranes, allergy to prostaglandins, history of asthma or glaucoma, evidence of fetal distress, or evidence of spontaneous labour. 
Interventions0.25 mg group: IC gel PGE2 0.25 mg.
0.5 mg group: IC gel PGE2 0.5 mg.
Control: IC placebo gel.
If the participant was not in labour after 12 hours observation, labour was induced by intravenous oxytocin infusion. If no appreciable change in the Bishop score was noted after the observation period, Laminaria digitata were inserted into the cervix and left in place for four hours before oxytocin induction. 
OutcomesWomen: CS, uterine hyperstimulation without FHR changes, maternal side-effects.
Fetal/infant: no outcomes reported. 
NotesMulticentre/single centre: single centre.
Supported in part by Upjohn Company, Kalamazoo, MI.
Setting: USA.
Additional outcomes reported: post treatment Bishop score, success of softening, time to labour, time to vaginal delivery, hypotension, fetal deep variable decelerations, prolonged bradycardia. 
Allocation concealmentA - Adequate 
StudyLegarth 1988 
MethodsRandomisation: RCT. Method of generating the allocation sequence not specified.
Allocation concealment: sealed envelopes.
Blinding: unclear.
Follow up: 9 women were excluded. 
Participants120 women were enrolled, 56 in the vaginal group and 57 in the IC group (9 women being excluded).
Eligibility: women with a cervix defined as being at least 1 cm in length, the internal cervical os just passable for one fingertip, singleton pregnancy, the fetus in the cephalic presentation, and a normal nonstress CTG test.
Exclusion: no information provided. 
InterventionsVaginal group: a suppository containing 2.5 mg PGE2 in a basis of 5 g of Witepsol S55 was placed in the posterior vaginal fornix.
IC group: 5 ml cervical gel containing 1 mg PGE2 in a basis of 5 g hydroxylpropylmethy 1 cellulose were applied within the cervical canal at the internal os by means of a 20 cm long and 4 mm thick plastic tube.
If labour was not established within 4 hours the application of the suppository or cervical gel was repeated.
Women who were not in labour the following morning and still had an unripe cervix were treated as the day before. If the cervix was ripe (internal os permitting entry of at least 1 finger or cervix shorter than 1 cm), induction by IV oxytocin was started using 0.4 milliunits per minute. This dose was increased by 1 milliunit every 15 minutes until satisfactory uterine activity was achieved or the dose level of oxytocin was 25 milliunits per minute. Amniotomy was performed when the isthmus os was more than 3 cm in diameter. 
OutcomesWomen: vaginal delivery not achieved within 24 hours, CS, oxytocin augmentation, instrumental vaginal delivery.
Fetal/infant: Apgar score < 7 at 5 minutes. 
NotesMulticentre/single centre: single centre.
Setting: Denmark.
Additional outcomes reported: CS within 48 hours after the induction and before the second stage of labour, delivery after 48 hours, fetal distress, cervical score (0, 4 and 24 hours after start of induction), interval from induction to labour, interval from induction to spontaneous rupture of the membranes, interval from induction to delivery, induction unsuccessful, oxytocin induction, amniotomy, delivery without oxytocin, spontaneous vaginal delivery, delivery with vacuum or forceps for fetal distress, Apgar score at 1 minute, Apgar score < 7 at 1 minute, Apgar score at 5 minutes, umbilical pH, umbilical pH < 7.15. 
Allocation concealmentA - Adequate 
StudyLien 1998 
MethodsRandomisation: RCT. Computer-generated sequence.
Allocation concealment: Coded drug boxes.
Blinding: 'double blind'.
Follow up: 2 participants were excluded for not meeting the inclusion criteria. 
Participants92 women were enrolled, 43 in experimental group, 47 in control group and 2 excluded.
Eligibility: a gestation age of at least 40 weeks 3 days, a Bishop score no more than 6, an amniotic fluid index > 5 cm, and a reactive nonstress test.
Exclusion: evidence of hyperstimulation or suspicious FHR patterns on antepartum testing, grand multiparity (at least 5 previous deliveries), nonvertex fetal presentation, multiple gestation, previous CS major uterine surgery, placenta previa, or other contraindications for vaginal delivery. 
InterventionsExperimental: IC gel PGE2 0.5 mg.
Control: IC placebo gel.
Study packets for each participant included a maximum of 4 dose study gel. Participants could receive a subsequent gel insertion in 3 to 4 days if they still met inclusion criteria. Elective induction would not be performed until 42 weeks' gestation unless the Bishop score was > 9 or an obstetric factor other than postdate pregnancy developed, necessitating labour induction. 
OutcomesWomen: CS, instrumental vaginal delivery, maternal nausea and vomiting, maternal diarrhoea, maternal side-effects.
Fetal/infant: Apgar score < 7 at 5 minutes. 
NotesMulticentre/single centre: multi-centre.
Setting: USA.
Additional outcomes reported: contractions, FHR deceleration, interval from study enrollment to delivery, hyperstimulation, birthweight, birthweight > 4000 g, maternal complications (chorioamnionitis, endometritis). 
Allocation concealmentA - Adequate 
StudyLopes 1991 
MethodsRandomisation: RCT. Method of generating the allocation sequence and of concealment of the allocation not specified.
Allocation concealment: unclear.
Blinding: unclear.
Follow up: no loss of participants reported. 
Participants100 women were enrolled, 24 in group 1, 26 in group 2, 28 in group 3 and 22 in group 4.
Eligibility: a medical indication for delivery within 48 hours, an unfavourable cervical state with a Bishop score equal or less than 5 points.
Exclusion: no information provided. 
InterventionsIf Bishop score equal or less than 3 points:
group 1: IC gel PGE2 0.5 mg (Prepidil).
group 2: IC PGE2 1.5 mg (Prostine) containing IC resorbable support.
If Bishop score 4-5:
group 3: IC gel PGE2 0.5 mg.
group 4: 2.25 mg PGE2 containing intravaginal administration of a resorbable support.
Induction of labour with intravenous oxytocin-amniotomy association was performed only when Bishop score reached 6 points. When Bishop score was below 6, a second administration of PGE2 was allowed 12 hours after the first application. 
OutcomesWomen: CS, uterine hyperstimulation with FHR changes, uterine hyperstimulation without FHR changes.
Fetal/infant: no outcomes reported. 
NotesMulticentre/single centre: single centre.
Setting: France.
Additional outcomes reported: increase of Bishop score, delivery within 12 hours, labour length, Apgar score.
The original paper was written in French and needed to be translated. 
Allocation concealmentB - Unclear 
StudyLyndrup 1991 
MethodsRandomisation: RCT. Method of generating the allocation sequence not specified.
Allocation concealment: sealed envelopes (nulliparous and parous separately).
Blinding: unclear.
Follow up: after allocation, 5 participants were excluded from the study material (4 participants did not fulfil the criteria for inclusion and 1 participant never received the proper treatment). Furthermore, in 5 participant s the protocol was violated. 
Participants130 women were enrolled, 64 in the IC group, 61 in the vaginal group, and 5 excluded.
Eligibility: women with singleton pregnancy, cephalic presentation, an unfavourable cervix (at least 1 cm long and the internal os not wider than just 1 fingertip), requiring induction of labour.
Exclusion: women already in labour, demonstrating a pathological nonstress test, with cardiopulmonary diseases, glaucoma, or previous uterine surgery exposing the uterine cavity or distorting the cervix. 
InterventionsIC: IC gel PGE2 0.5 mg, once a day.
Vaginal group: PGE2 2.5 mg in vaginal pessaries. The pessary was placed in the posterior vaginal fornix, and if labour was not established within 3 hours, application was repeated.
If the participant did not deliver within the first 24 hours and labour was not established, further induction depended on the cervical status at the beginning of the next 24-hour period. If the cervix was still unfavourable (at least 1 cm long and internal os not wider than 1 fingertip), the procedure was repeated. If the cervix was now favourable further induction was performed using IV oxytocin titration (starting with 3 mU/min and stepwise increasing the dose to a maximum of 30 mU/minute). 
OutcomesWomen: CS, oxytocin augmentation, instrumental vaginal delivery, women not satisfied.
Fetal/infant: Apgar score < 7 at 5 minutes. 
NotesMulticentre/single centre: single centre.
Setting: Denmark.
Additional outcomes: oxytocin induction, amniotomy, spontaneous vaginal delivery (within 2 days or after 2 days), continuation of pregnancy (considering vaginal delivery as the event or onset of labour as the event), duration of labour (life table analysis), improvement in cervical ripening (after 3 or 24 hours), Apgar score at 1 minute, pH in umbilical artery, SEB in umbilical artery, vaginal discomfort. 
Allocation concealmentA - Adequate 
StudyMcKenna 1999 
MethodsRandomisation: RCT. Allocation sequence generated by a table of random numbers.
Allocation concealment: central randomisation.
Blinding: 'double blind'.
Follow up: 4 participants were excluded after randomisation for not meeting the inclusion criteria at the time of planned gel administration. 
Participants65 women were enrolled, 30 in experimental group and 31 in control group.
Eligibility: at least 37 completed gestational weeks, maternal age of at least 18 years, an unfavourable cervix for induction (Bishop score 8 or less), a well-dated pregnancy, and lack of a current indication for induction of labour.
Control: multiple gestations, contraindications to trials of labour, insulin-dependent diabetes, or chronic hypertension. 
InterventionsExperimental: IC PGE2 0.5 mg as outpatient, once.
Control: IC placebo as outpatient, once. 
OutcomesWomen: CS, PPH, uterine hyperstimulation with FHR changes.
Fetal/infant: NICU, Apgar score < 7 at 5 minutes. 
NotesMulticentre/single centre: single centre.
Setting: USA
Additional outcomes reported: days to admission, inductions, change in Bishop score, labour duration, delivery within 2 days, birthweight, maternal or neonatal stay, hemoglobin change, infectious morbidity. 
Allocation concealmentA - Adequate 
StudyMilliez 1993 
MethodsRandomisation: RCT. Method of generating the allocation sequence not specified.
Allocation concealment: by choosing an envelope.
Blinding: no information provided.
Follow up: no loss of participants reported. 
Participants84 women were enrolled, 42 in each group.
Eligibility: high-risk pregnancy, indication for induction of labour, Bishop score less than 5.
Exclusion: breech presentation, previous CS, uterine contractions. 
Interventions0.5 mg group: IC gel PGE2 0.5 mg, 1 dose. Participants who did not in labour 12 hours after application had labour induced with oxytocin, irrespective of their Bishop score, or earlier than 12 hours in case of maternal or fetal distress.
0.25 mg group: IC gel PGE2 0.25 mg. The participants who did not labour after the first ripening procedure had repeated daily application of 0.25 mg PGE2 until spontaneous onset of labour occurred or induction of labour with oxytocin was decided. Labour was induced because of a Bishop score improved to 6 or more, or because of a rapid deterioration of the maternal or fetal condition, necessitating a prompt delivery and requiring therefore a break in the sequence of repeated maturations of the cervix. 
OutcomesWomen: CS. uterine hypertension with FHR changes.
Fetal/infant: no outcomes reported. 
NotesMulticentre/single centre: single centre.
Setting: France.
Additional outcomes reported: cervical ripening, uterine contraction, spontaneous onset of labour, oxytocin induction, FHR decelerations, birthweight, Apgar score at 1 minute, Apgar score at 5 minutes. 
Allocation concealmentB - Unclear 
StudyNICHHD 1994 
MethodsRandomisation: RCT, computer-assigned randomisation scheme arranged by the data coordinating centre. Randomisation was stratified by the clinical site and week of gestation.
Allocation concealment: unclear.
Blinding: both the participants and the investigators were blinded to the study groups.
Follow up: no loss of participants reported. 
Participants265 women were enrolled, 174 in experimental group and 91 in control group.
Eligibility: term between 280 and 301 days.
Exclusion: medical or obstetric complications requiring induction of labour, CS, or frequent monitoring of maternal or fetal condition; an estimated fetal weight exceeding 4500 gm by clinical or ultrasonographic examination; Bishop score (maximum score of 13) of 7 of greater; nonstress test not reassuring (nonreactive or showing decelerations); the largest pocket of amniotic fluid < 2.0 cm. 
InterventionsExperimental: IC gel PGE2 0.5 mg (1 dose) followed 12 hours later with oxytocin.
Control: IC placebo gel (1 dose) followed 12 hours later with oxytocin.
Subjects underwent induction within 24 hours after randomisation. When clinically feasible, amniotomy was performed before the administration of oxytocin. If amniotomy was not feasible, oxytocin infusion was initiated according to uniform protocol. If the participant had not entered the active phase of labour after 24 hours of oxytocin administration, a CS was performed or induction of labour was continued for a longer time. 
OutcomesWomen: CS, serious neonatal morbidity or perinatal death, serious maternal morbidity or death, uterine hyperstimulation without FHR changes, meconium stained liquor, use of blood transfusion, maternal death.
Fetal/infant: Apgar score < 4 at 5 minutes, perinatal death. 
NotesMulticentre/single centre: multi-centre.
Setting: USA.
Additional outcomes reported: intracranial hemorrhage, mechanical ventilation, nerve injury, seizures, babies with at least 1 adverse outcome, randomisation-delivery interval, maternal infection, vaginal delivery, late decelerations in labour, meconium aspiration pneumonia, birthweight.
Data only presented on ICPG compared with placebo presented. Expectant management arm excluded. 
Allocation concealmentB - Unclear 
StudyNager 1987 
MethodsRandomisation: RCT, using a random-number generator keyed to participant entry number.
Allocation concealment: unclear.
Blinding: unclear.
Follow up: 1 participant was lost to follow up. 
Participants35 women were enrolled, 19 in experimental group and 15 in control group (was there 1 woman lost?).
Eligibility: women with medical, obstetric, or fetal indications for labour induction and had an unfavourable Bishop score, less than or equal to 4.
Exclusion: women with a history of asthma, glaucoma, hypersensitivity to prostaglandins, vaginal bleeding, ruptured membranes, labour, previous caesarean delivery, or previous attempt at labour induction in this pregnancy. 
InterventionsExperimental: women were given IC 0.5 mg PGE2 in a total volume of 2.5 ml IC using a 12 FG Luer mount catheter. The catheter was passed transcervically under direct visualisation or by palpation until resistance or the amniotic membranes were reached. The 2.5 ml of gel containing the preparation was then discharged from a preloaded syringe attached to the catheter.
Control: no medication.
After 12 hours, oxytocin induction was begun by specified protocol, beginning at 0.4 mU/minute and escalating every 20 minutes to a maximal infusion rate of 20 mU/minute. For purpose of standardisation amniotomy was performed when the active phase labour was achieved. Continuos uterine activity and FHR monitoring was used for all participant . All participants received at least 12 hours of oxytocin before unsuccessful induction or failed labour was diagnosed. 
OutcomesWomen: CS.
Fetal/infant: no outcomes reported. 
NotesMulticentre/single centre: Single centre.
Setting: USA.
Additional outcomes reported: Bishop score (t =12 hours), delivery (from t = 0 hour), induction to delivery, maximum dose of oxytocin, duration of oxytocin, onset of labour (from t = 0 hour), onset of labour (from t = 0 hour), rupture of membranes (from t = 0 hour), estimated blood loss (ml), CS for failed induction, spontaneous rupture of membranes, labour before oxytocin, delivery before oxytocin, labour before end of 12-hour induction period, Apgar score at 1 minute, Apgar score at 5 minutes, fetal weight, suspected uterine hypertonus. 
Allocation concealmentB - Unclear 
StudyNimrod 1984 
MethodsRandomisation: RCT, method of generation of the allocation sequence unclear.
Allocation concealment: identical syringes dispensed by the hospital pharmacy in sequential order when requested.
Blinding: ''double blind'.
Follow up: no loss of participants reported. 
Participants45 women were enrolled, 15 in each group.
Eligibility: a modified Bishop score of 4 or less.
Exclusion: contractions present during the evaluation period. 
InterventionsExperimental group 1: IC gel PGE2 0.5 mg (1 dose).
Experimental group 2: IC gel PGE2 0.25 mg (1 dose).
Control: IC placebo gel (1 dose). 
OutcomesWomen: CS, uterine hyperstimulation with FHR changes, uterine hyperstimulation without FHR changes, nausea, diarrhoea.
Fetal/infant: serious neonatal morbidity or death, NICU admission. 
NotesMulticentre/single centre: single centre.
Setting: Canada.
Additional outcomes reported: spontaneous labour, length of labour, Apgar score at 1 minute, Apgar score at 5 minutes, birthweight, congenital anomaly.
Comparison of ICPG to ICPG data not presented as both doses fall into low dose category (0.25 and 0.5 mg). 
Allocation concealmentA - Adequate 
StudyNoah 1987 
MethodsRandomisation: RCT, method of generation of the allocation sequence unclear.
Allocation concealment: unclear.
Blinding: open study.
Follow up: 4 women (3 gel and 1 control) excluded. 
Participants820 women were enrolled, 416 in experimental group and 404 in control group.
Eligibility: Bishop score of 0-5, a medical-obstetrical indication for labour induction, intact membranes.
Exclusion: no information provided. 
InterventionsExperimental: IC gel PGE2 0.5 mg (1 dose).
Control: no treatment.
At the end of 12 hours, all participants not in labour were treated with an intravenous infusion of oxytocin as the 'initial' induction attempt. Oxytocin was started at 1.0 mU/minute and escalated at 30 to 60 minute intervals as required to a maximum dose of 16 mU/minute. Amniotomy was performed after labour had started. If labour had not started within 12 hours, the attempt at labour induction could be judged a failure. 
OutcomesWomen: CS, serious maternal morbidity or death, vomiting, diarrhea.
Fetal/infant: serious neonatal morbidity or death, Apgar score < 7 at 5 minutes.

Keiback 1986 - instrumental delivery: 5/50 in PGE2 group and 10/50 placebo group.
Kristoffersen 1986 - instrumental delivery: 7/25 in PGE2 group and 5/25 placebo group. 
NotesMulticentre/single centre: Multicentre study.
Setting: Europe and Africa (1983-1984).
Additional outcomes reported: successful induction of labour on the initial attempt, the mode of delivery, Bishop score progression during 1st 12 hours, induction - delivery interval, FHR changes and unclassified fetal distress, uterine contractile abnormalities, uterine hyperstimulation, Apgar score < 7 at 1 minute, alkaline phosphatase, glutamic oxalacetic transaminase, creatinine, uric acid, complete blood counts and urinalysis.
Some individual centres published their own data. These data have not been entered into the meta-analysis, as it is already reported in the Noah 1987 paper which is the full multi-centre trial report. However, some centres (Keiback 1986; Kristoffersen 1986) published additional data. These additional data have not been entered into Review Manager, but are presented in this table (outcomes) and in the text of the review (Description of studies). 
Allocation concealmentB - Unclear 
StudyNuutila 1995 
MethodsRandomisation: RCT. No details given.
Allocation concealment: unclear.
Blinding: unclear.
Follow up: no loss of participants reported. 
Participants45 women were enrolled, 24 in experimental group and 21 in control group.
Eligibility: otherwise healthy, admitted due to pre-eclampsia which was defined as blood pressure constantly > 140/90 mmHg and proteinuria > 0.5 g/L, singleton, vertex presentation, unripe cervix (Bishop score 5 or less), and no sign of fetal compromise.
Exclusion: no information provided. 
InterventionsExperimental: IC gel PGE2 0.5 mg.
Control: IC placebo gel.
If there were no contractions, or if Bishop score remained 5 or less after 6 hours, a second gel was applied. The labour was induced, or augmented if regular contractions had begun and Bishop score was more than 5, by amniotomy and/or oxytocin infusion (5 IU in 500 mL). 
OutcomesWomen: CS, maternal side-effects, nausea, vomiting, diarrhoea.
Fetal/infant: Apgar score < 7 (at 5 minutes?). 
NotesMulticentre/single centre: single centre.
Setting: Finland.
Additional outcomes reported: Bishop score, interval from treatment to labour, interval from treatment to delivery, spontaneous labour, induction failure, umbilical artery pH, birthweight. 
Allocation concealmentA - Adequate 
StudyNuutila 1996 
MethodsRandomisation: RCT, method of generation of the allocation sequence unclear.
Allocation concealment: by sealed opaque envelopes.
Blinding: no information provided.
Follow up: no loss of participants reported. 
Participants110 women were enrolled, 35 in group A, 36 in group B and 39 in group C.
Eligibility: with a decision of induction of labour, a high risk of pregnancy, unfavourable cervix (Bishop score 5 or less), singleton, intact membranes, vertex presentation.
Exclusion: hemorrhage during the third trimester of pregnancy, asthma, glaucoma and a history of hypersensitivity to prostaglandins.
Unfavourable cervix (BS < 6) and indication for labour induction. 
InterventionsGroup A: IC gel PGE2 0.5 mg (2 doses, 6 hourly).
Group B: intravaginal gel PGE2 1 mg.
Group B: intravaginal gel PGE2 2 mg.
The gel was reapplied, maximally twice at 6-hour intervals, if Bishop score remained 5 or less and if there were no regular contractions. If labour had not started but Bishop scores were more than 5, induction was performed by amniotomy and/or oxytocin infusion (5 IU in 500 mL with accelerating infusion rate 5-20 drops/minute corresponding to up to 10 mIU/minute). 
OutcomesWomen: CS, uterine hyperstimulation with FHR changes, maternal side-effects.
Fetal/infant: Apgar score < 7 (at 5 minutes?). 
NotesMulticentre/single centre: single centre.
Setting: Finland.
Additional outcomes reported: ripening failure, ripening time, labour time, umbilical artery pH 7.15 or less. 
Allocation concealmentA - Adequate 
StudyOttinger 1998 
MethodsRandomisation: RCT. Allocation sequence by a table of random numbers.
Allocation concealment: sealed, opaque, numbered envelopes.
Blinding: no information provided.
Follow up: two women were excluded for breach of protocol. 
Participants92 women were enrolled, 45 in the IC group, 45 in the vaginal group and 2 excluded.
Eligibility: (1) age 14 to 40 years, (2) singleton gestation, (3) cephalic presentation, (4) intact membranes, (5) reassuring fetal testing (reactive nonstress test or biophysical profile score at least 6), (6) Bishop score 8 or less, and (7) requiring induction of labour for medical or obstetric indications.
Exclusion: (1) active vaginal bleeding, (2) history of adult asthma or glaucoma, (3) cerclage (this pregnancy), or (4) multifetal gestations.
Prior CS (if low transverse or low vertical without extension) was not an exclusion criteria. 
InterventionsIC group: IC PGE2 0.5 mg gel. A repeat IC gel (for a maximum 2 doses) was placed at 6 hours if spontaneous labour or rupture of membranes had not occurred.
Intravaginal group: intravaginal PGE2 10 mg controlled-release pessary. The pessary was placed in the posterior vaginal fornix and removed after 12 hours. The pessary was removed before 12 hours if spontaneous labour (contractions every 2 to 3 minutes), tachysystole (contractions every 1 to 2 minutes), or rupture of membranes occurred. Vaginal pessaries were removed at least 30 minutes before the start of oxytocin.
If spontaneous labour had not begun by 12 hours after treatment, oxytocin infusion was begun at 1 mU and increased every 15 to 20 minutes until adequate labour was achieved. All participants were given at least 12 hours of oxytocin. 
OutcomesWomen: vaginal delivery not achieved within 24 hours, CS, uterine hyperstimulation with FHR changes, uterine hyperstimulation without FHR changes, oxytocin augmentation.
Fetal/infant: Apgar score < 7 at 5 minutes. 
NotesMulticentre/single centre: single centre.
Setting: USA.
Additional outcomes reported: vaginal delivery, time intervals from start of induction to various labour end points (rupture of membranes, complete dilatation, vaginal delivery), birthweight, Apgar scores at 1 minute, Apgar scores at 5 minutes, Apgar score < 7 at 1 minute. 
Allocation concealmentA - Adequate 
StudyOwen 1991 
MethodsRandomisation: RCT. Method of generation of the allocation sequence unclear.
Allocation concealment: Randomisation was performed in the pharmacy and directed by the contents of the next sealed envelope.
Blinding: 'double blind'.
Follow up: no loss of participants reported. 
Participants100 women were enrolled, 47 in experimental group and 53 in control group.
Eligibility: a maternal or fetal indication for labour induction, a Bishop score no more than 4, no evidence of fetal distress, and intact membranes.
Exclusion: hypersensitivity to prostaglandins, history of asthma or glaucoma, vaginal bleeding, failure of a previous attempt at labour induction, contraindications to labour induction, or spontaneous contractions. 
InterventionsExperimental: IC gel PGE2 0.5 mg.
Control: IC gel placebo.
After a monitored 12 hour interval oxytocin was started, unless spontaneous labour had begun. 
OutcomesWomen: uterine hyperstimulation with FHR changes, CS, nausea, vomitting, diarrhoea.
Fetal/infant: Apgar score < 7 at 5 minutes. 
NotesMulticentre/Single centre: single centre.
Setting: USA.
Additional outcomes reported: Bishop score change, failed labour induction, dystocia, interval from treatment to delivery, fever, umbilical arterial pH < 7.2, fetal distress. 
Allocation concealmentA - Adequate 
StudyPeccerillo 1995 
MethodsRandomisation: RCT. Method of generation of the allocation sequence unclear.
Allocation concealment: unclear.
Blinding: unclear.
Follow up: 2 participants were excluded. 
Participants69 women were enrolled, 31 in experimental group, 36 in control group and 2 excluded.
Eligibility: presenting for induction, at least 37 weeks' gestation, Bishop score no more than 6.
Exclusion: no information provided. 
InterventionsExperimental: IC PGE2 0.5 mg.
Control: Intravaginal PGE2 2.5 mg.
Subsequent doses were administer every 4 hours followed by oxytocin augmentation. 
OutcomesWomen: CS.
Fetal/infant: no outcomes reported. 
NotesMulticentre/Single centre: single centre.
Setting: USA.
Additional outcomes reported: change in Bishop score, duration of induction. 
Allocation concealmentB - Unclear 
StudyPerez Picanol 1990 
MethodsRandomisation: RCT. Method of generation of the allocation sequence unclear.
Allocation concealment: unclear.
Blinding: no information provided.
Follow up: no loss of participants reported. 
Participants71 women were enrolled, 35 in experimental group and 36 in control group.
Eligibility: termed pregnancy, premature rupture of membranes < 12 hours, and low Bishop score (no more than 4).
Exclusion: no information provided. 
InterventionsExperimental: IC gel PGE2 0.5 mg.
Control: no treatment.
6 hours later a conventional administration of oxytocin was started in both groups for stimulation or induction of labour. 
OutcomesWomen: uterine hyperstimulation with FHR changes, CS.
Fetal/infant: NICU. 
NotesMulticentre/single centre: single centre.
Setting: Spain.
Additional outcomes reported: change in Bishop score, administration-delivery interval, oxytocin administration-delivery interval, vaginal delivery within 12 hours, Apgar score at 1 and 5 minutes, umbilical artery pH. 
Allocation concealmentB - Unclear 
StudyPerry 2003 
MethodsRandomisation: RCT. Method of generation of the allocation sequence unclear.
Allocation concealment: Shuffled opaque sealed envelopes were placed into a covered box with subsequent blind retrieval.
Blinding: with the exception of the resident placing the dinoprostone, the staff and participants were blinded to the site of placement.
Follow up: no loss of participants reported. 
Participants63 women were enrolled, 33 in experimental group and 30 in control group.
Eligibility: admitted to the labour and delivery unit for dinoprostone induction with a singleton, cephalic fetus greater than or equal to 36 weeks' gestation with an initial Bishop score less than 6.
Exclusion: cervical dilatation greater than 2 cm, a history of prior caesarean delivery or hysterotomy, ruptured membranes, intrauterine growth restriction, known fetal anomalies, a nonreassuring FHR pattern, prior use of cervical ripening agents in the current pregnancy, other contraindications to vaginal delivery. 
InterventionsExperimental group: IC sustained-release PGE2 10 mg insert.
Control group: Intravaginal (posterior fornix) insertion of the same sustained-release PGE2 insert.
The dinoprostone insert remained in place for 12 hours or until labour ensured, at which time augmentation with oxytocin was initiated. In participants requiring further cervical ripening, subsequent doses were placed in the posterior fornix. 
OutcomesWomen: CS, oxytocin augmentation.
Fetal/infant: no outcomes reported. 
NotesMulticentre/single centre: single centre.
Setting: USA.
Additional outcomes reported: change in Bishop scores, time to delivery, time to initial request for pain medications, time to ruptured membranes, artificial rupture of membranes, time to active labour, tachysystole, hyperstimulation, maternal fever, birthweight, Apgar scores, umbilical artery pH. 
Allocation concealmentA - Adequate 
StudyPoulsen 1991 
MethodsRandomisation: RCT. Block of 10 randomisation.
Allocation concealment: sealed envelopes.
Blinding: open study.
Follow up: no loss of participants reported. 
Participants226 women were enrolled, 116 in the IC gel group and 110 in the vagitory group.
Eligibility: at term (259 to 303 days menstrual age), healthy, singleton pregnancy in a cephalic presentation, no history of previous CS or cervical conization and not in labour, an unfavourable cervix according to a modified cervical score of no more than 4 points.
Exclusion: no information provided. 
InterventionsIntracervical gel group: 0.5 mg PGE2 in 2 ml of viscous slow-release gel applied intracervically.
Vaginal group: 2.5 mg PGE2 in a vagitory placed in the posterior vaginal fornix.
When labour became established, the membranes were ruptured artificially as soon as possible. At 12 hours after administration of the drug, the woman was reassessed and if possible the membranes ruptured. Oxytocin infusion (10 IE/500 ml isotonic saline) was commenced 2 hours later when indicated. If rupture of the membranes was not feasible (cervical score no more than 4 points), the women was given the same substance again using the same observation schedule. The cervix was assessed again at 24 hours if required. Otherwise, routine labour ward management at the obstetricians' discretion was applied. 
OutcomesWomen: vaginal delivery not achieved within 24 hours, CS,uterine hyperstimulation without FHR changes, nausea, diarrhea, meconium stained liquor, instrumental vaginal delivery (figures not given).
Fetal/infant: no outcomes reported. 
NotesMulticentre/single centre: multi-centre.
Setting: Denmark and Iceland.
Additional outcomes reported: abnormal FHR, contractions, strong contractions, analgesic, in labour/delivery by 12 hours, in labour/delivery by 24 hours, total not in labour, delivery (at no more than 12 hours, at 12-24 hours, at 24-36 hours, at 36-48 hours), oxytocin requirement, Apgar scores at 1 and 5 minute, blood loss > 500 ml, neonatal illness, time from priming to rupture of membranes, time from priming to established labour and priming to delivery, fetal death. 
Allocation concealmentA - Adequate 
StudyRamsey 2003 
MethodsRandomisation: a prospective randomised clinical trial. Randomisation was done independently through the central hospital pharmacy using dynamic allocation with stratification by parity (primiparous vs multiparous) and initial Bishop score (no more than 2 or > 2).
Allocation concealment: unclear.
Blinding: blinding of caregiver.
Follow up: no loss of participants reported. 
Participants111 women were enrolled, 35 in dinoprostone 0.5 mg gel intracervically group (1), 38 in dinoprostone 10 mg intravaginally insert group (2) and 38 in misoprostol group (3). Groups 1 and 2 presented in the review.
Eligibility: (1) an unfavorable cervical Bishop score equal to or less than 5, (2) a singleton pregnancy with vertex presentation and no contraindication to vaginal delivery, (3) the absence of spontaneous uterine contractions (ie, < 4 spontaneous contractions per hour), and (4) a reactive nonstress test.
Exclusion: (1) a known hypersensitivity to prostaglandins, (2) ruptured membranes, (3) suspected chorioamnionitis, (4) parity of > 5, (5) a previous caesarean delivery or history of uterine surgical procedures, and (6) previous attempted induction of labour for this pregnancy. 
InterventionsDinoprostone gel group: dinoprostone gel 0.5 mg administered intracervically initially, with 1-time repeat dosing 6 hours later.
Dinoprostone insert group: dinoprostone vaginal insert 10 mg administered into the posterior fornix for a total 12 hours.
Misoprostol group: misoprostol 50 µg intravaginally in the posterior fornix initially, with 1-time repeat dosing 6 hours later.
All study candidates were admitted to the labour and delivery unit 12 hours before the scheduled induction of labour; cardiotocography was performed to rule out fetal distress and the presence of uterine contractions.
Women with an established contraction pattern of > 3 contractions in 10 minutes, with rupture of membranes, or with an abnormality of the fetal heart tracing did not undergo redosing with the study agent. The dinoprostone vaginal insert was continued in the setting of an established contraction pattern in the absence of rupture of membranes or an abnormality of the fetal heart tracing.
Participants who were not in an adequate labour pattern after the preinduction interval received standard oxytocin infusion at an initial rate of 2 mU/minute, with 2 mU/minute incremental increases at 20-minute intervals to a maximum of 30 mU/minute until an adequate labour pattern (at least 200 Montevideo units every 10 minutes, as measured by intrauterine pressure catheter) was obtained. Participants with active-phase labour (at least 4 cm dilation with regular uterine contractions) with arrest of dilation (no change in cervical dilation for at least 2 hours), despite adequate labour pattern contractions received oxytocin augmentation according to the above protocol. Continuous electronic FHR and tocodynamic monitoring was used throughout labour. Standardised intrapartum treatment guidelines were used for all participants . Women in whom uterine hyperstimulation developed received a single dose of subcutaneous terbutaline (0.25 mg), along with a position change and oxygen administration. Participants who demonstrated no significant cervical change during the initial 24-hour period were retreated with the original cervical ripening regimen for an additional 12 hours before the oxytocin therapy was reinitiated. 
OutcomesWomen: (vaginal?) delivery not achieved within 24 hours, uterine hyperstimulation with FHR changes, CS, cervix unfavorable after 12 hours, oxytocin augmentation, meconium stained liquor (meconium passage), PPH.
Fetal/infant: NICU admission. 
NotesMulticentre/single centre: single centre.
Setting: USA.
Commercially funded by Upjohn Co, Kalamazoo, Mich.
Additional outcomes reported:
For women: change in Bishop score over initial 12 hours, time to active labour, time to complete dilation, time to delivery, time to vaginal delivery, total hours of oxytocin infusion, total amount of oxytocin, chorioamnionitis, cost, the cost that was incurred per participant to achieve a 1-point change in the cervical Bishop score, complete dilation within 24 hours, delivery within 48 hours of treatment initiation, additional 12 hours of cervical ripening for a persistent unfavourable cervix after the initial 24-hour inductions, overall mean cost per participant, incidence of cardiotocographic abnormalities (overall, hypertonus, tachysystole, hyperstimulation syndrome) during the initial 24 hours of induction, mean number of abnormal cardiotocographic events (overall, hypertonus, tachysystole, hyperstimulation syndrome) per participant during the initial 24 hours of induction, time to abnormal cardiotocographic events occurring, abnormal cardiotocographic patterns within 6 hours of initial dosing.
For neonatal outcomes: birthweight, Apgar score at 1 minute, Apgar score at 5 minutes, venous cord pH, aterial pH, supplemental oxygen. 
Allocation concealmentB - Unclear 
StudyRath 1999 
MethodsRandomisation: RCT, method of generation of the allocation sequence unclear.
Allocation concealment: unclear.
Blinding: unclear.
Follow up: 2 women were excluded. 
Participants470 women were enrolled. The outcomes of 242 in the IC group and 226 in the intravaginal group were analysed.
Eligibility: Bishop score 3-4, singleton, cephalic, primiparous, intact membranes, live fetus, ruptured membranes, 34 to 42 gestational weeks, diabetes or hypertension.
Exclusion: malpresentations, multiparous, previous classical CS, no reassuring CTG. 
InterventionsIC group: IC gel PGE2 0.5 mg.
Intravaginal group: intravaginal gel PGE2 2 mg.
The application were repeated at intervals of 6 hours if necessary. 
OutcomesWomen: vaginal delivery not achieved within 24 hours, CS.
Fetal/infant: no outcomes reported. 
NotesMulticentre/single centre: multi-centre.
Setting: Germany.
Additional outcomes reported: cervical ripening effect, induction-delivery interval, hyperstimulation, Apgar score 7 or less at 5 minutes, cord blood pH < 7.10, cord blood pH < 7.20, cord blood pH < 7.00.
The original paper was written in German and needed to be translated.
Data from trial - uterine hyperstimulation with and without FHR changes: IC = 24/242; intravaginal = 21/226. Apgar score less than or = to 7: IC = 3/242; intravaginal = 6/226. Cord blood < 7.10: IC = 3/242; intravaginal = 2/226, < 7.20: IC = 19/242; intravaginal = 27/226, < 7.0: IC = 0/242; intravaginal = 1/226. These data have not been entered into Review Manager. 
Allocation concealmentB - Unclear 
StudyRichardson 1991 
MethodsRandomisation: RCT. Method of generation of the allocation sequence unclear.
Allocation concealment: unclear.
Blinding: 'double blind'.
Follow up: no loss of participants reported. 
Participants48 women were enrolled, 21 in experimental group and 27 in control group.
Eligibility: cervix < 2 cm dilated and < 50% effaced, > 37 weeks' gestation, intact membranes, vertex presentation, singleton, and a reactive nonstress test.
Exclusion: no information provided. 
InterventionsExperimental: IC gel PGE2 0.5 mg.
Control: IC placebo gel.
Oxytocin induction of labour was followed 4 hours after treatment. 
OutcomesWomen: CS.
Fetal/infant: no outcomes reported. 
NotesMulticentre/single centre: single centre.
Setting: USA.
Additional outcomes reported: fetal distress, vaginal delivery. 
Allocation concealmentB - Unclear 
StudyRix 1996 
MethodsRandomisation: a prospective, randomised study. Method of generation of the allocation sequence unclear.
Allocation concealment: by sealed, numbered envelopes.
Blinding: unclear.
Follow up: 27 participants dropped out, 15 in IC gel group and 12 in vaginal tablets group. 
Participants208 women were enrolled, 110 in IC gel group and 98 in vaginal tablets group.
Eligibility: Bishop score not greater than 5, a fetus in cephalic presentation, intact membranes and no contraindications to prostaglandin administration.
Exclusion: previous precipitate labour, Potter syndrome. 
InterventionsExperimental: IC PGE2 gel 0.5 mg.
Control: PGE2 vaginal tablets 3 mg.
6 and 12 hours later the procedure was repeated and continued the following day for a maximum of 6 applications, if necessary, until ripening of the cervix was seen, defined by cervical dilatation beyond 3 cm, or labour induced.
Amniotomy was performed if no further progress was seen once ripening was obtained, followed one hour later by IV oxytocin stimulation, if necessary. 
OutcomesWomen: CS, instrumental vaginal delivery (figures not given)
Fetal/infant: serious neonatal morbidity (birth asphyxia). 
NotesMulticentre/single centre: single centre.
Setting: Denmark.
Commercially funded by Upjohn Co, Kalamazoo, Mich.
Additional outcomes reported: ripening of the cervix (6, 12, 24, 36 and 42 hours from start of induction), cumulative number of deliveries during the study shown by 6 hours interval, mean induction-delivery intervals, amniotomy, oxytocin stimulation (unclear definition), pethidine analgesia, precipitous active phase of delivery, instrumental delivery, augmentation of second stage labour by oxytocin, atonic postpartum bleeding, failed induction of labour, gastrointestinal symptoms, vaginal pain and birth weight. 
Allocation concealmentA - Adequate 
StudySeeras 1995 
MethodsRandomisation: RCT. Method of generation of the allocation sequence unclear.
Allocation concealment: sealed, opaque envelopes.
Blinding: unclear.
Follow up: no loss of participants reported. 
Participants68 women were enrolled, 37 in the IC group and 31 in the vaginal group.
Eligibility: admitted for elective induction of labour. a gestational age > 37 completed weeks, intact membranes, not in labour.
Exclusion: previous CS, surgery to the uterine corpus, malpresentation and other contraindications to vaginal delivery, presence of active liver disease, severe cardiac disease, glaucoma, severe asthma or allergy to prostaglandin. 
InterventionsIC group: IC gel PGE2 0.5 mg 6 hourly, max 3 doses.
Vaginal group: intravaginal gel PGE2 2 mg 6 hourly, max 3 doses. 
OutcomesWomen: CS, serious maternal morbidity or death, oxytocin augmentation, uterine hyperstimulation without FHR changes, epidural analgesia, instrumental vaginal delivery, nausea and vomiting, PPH.
Fetal/infant: serious neonatal morbidity or perinatal death, Apgar score < 7 at 5 minutes, NICU admission, perinatal death. 
NotesMulticentre/single centre: single centre.
Setting: UK.
Additional outcomes reported: successful induction, oxytocin induction, induction-labour interval, induction-delivery interval, spontaneous vertex delivery, delivery within 24 hours, abnormal FHR, Apgar score < 7 at 1 minute, use of pethidine. 
Allocation concealmentA - Adequate 
StudyStempel 1997 
MethodsRandomisation: RCT. Computer-generated allocation sequence.
Allocation concealment: participants were allocated by use of a pharmacy-prepared randomisation list.
Blinding: no information provided.
Follow up: no loss of participants reported. 
Participants83 women were enrolled, 39 in the cervical gel group and 44 in the vaginal gel group.
Eligibility: requiring cervical ripening for the induction of labour, singleton pregnancy with live fetus in the vertex presentation a Bishop score not greater than 6.
Control: pregnancy with an contraindication for gel use: hypersensitivity, placenta previa, malpresentation, unexplained vaginal bleeding, regular contractions in spite of an unripe cervix, or evidence of fetal distress. 
InterventionsIC gel group: IC gel PGE2 0.5 mg.
Intravaginal gel group: intravaginal gel PGE2 5 mg.
Gel administration could be repeated twice at 6-hour intervals if the cervix remained unfavourable and the participant was not having contractions. Oxytocin was administered 6 to 12 hours after the last gel. Oxytocin was started at 1 to 2 mIU and increased by 1 to 2 mIU every 15 minutes until adequate labour was achieved. 
OutcomesWomen: CS, uterine hypertension with FHR changes, oxytocin augmentation.
Fetal/infant: no outcomes reported. 
NotesMulticentre/single centre: single centre.
Setting: USA.
Additional outcomes reported: spontaneous labour, the need for and success of oxytocin induction of labour, failed induction, the interval from first gel insertion to oxytocin imitation, Bishop score change, duration of labour, vaginal delivery, birthweight, Apgar score at 1 minute, Apgar score at 5 minutes, pH umbilical vein, pH umbilical artery. 
Allocation concealmentA - Adequate 
StudyStiver 1991 
MethodsRandomisation: RCT, method of generation of the allocation sequence unclear.
Allocation concealment: unclear.
Blinding: 'double blind'.
Follow up: no loss of participants reported. 
Participants28 women were enrolled, 15 in group A and 13 in group B.
Eligibility: primigravid, at least 37 weeks' gestation with indications for delivery and Bishop score 5 or less.
Exclusion: no information provided. 
InterventionsGroup A: IC gel PGE2 0.2 mg.
Group B: IC gel PGE2 0.5 mg.
Same application was repeated at intervals of 6 hours until spontaneous rupture of membranes or labour occurred, dilatation was at least 4 cm, or 5 doses were given, at which time oxytocin induction or augmentation was begun. 
OutcomesWomen: CS.
Fetal/infant: no outcomes reported. 
NotesMulticentre/single centre: single centre.
Setting: USA.
Additional outcomes reported: spontaneous labour, doses needed to achieve 75% effacement, doses needed to reach at least 3 cm dilatation, Bishop score 9 or greater after each dose.
Abstract only. 
Allocation concealmentB - Unclear 
StudyStrobelt 2006 
MethodsRandomisation: a prospective randomised study, with parity-based randomisation.
Allocation concealment: not used. The participants were allocated by a parity-based open randomisation list.
Blinding: unclear.
Follow up: no loss of participants reported. 
Participants107 women were enrolled, 56 in experimental group and 51 in control group.
Eligibility: single pregnancy, cephalic presentation, gestational age at least 37 and equal to or less than 41 weeks, Bishop score at admission equal to or less than 4.
Exclusion: PROM, history of previous CS, vaginal bleeding, suspicious or ominous non-stress test at admission, placenta previa, chorioamnionitis, HELLP syndrome, sonographically expected birth weight > 4000 g, and maternal clinical contraindications to the administration of PGE2 analogs. 
InterventionsExperimental: dinoprostone 10-mg vaginal insert , with the continuous, controlled release of 0.3 mg of dinoprostone per hour. Vaginal insert was removed in the case of PROM, onset of labour, or abnormal CTG pattern. Participants with PROM underwent oxytocin induction and IV ampicillin administration 2 hours thereafter if not in labour. Participants with intact membranes not labouring after 12 hours from induction received 2 mg of dinoprostone vaginal gel for at least 2 applications with an 8-hour interval if Bishop score was still 0-4, or underwent amniotomy and eventually oxytocin infusion if Bishop score had become equal to or more than 5.
Control: dinoprostone 0.5-mg cervical gel. Control participants received at least 2 doses of 0.5-mg dinoprostone cervical gel under sterile speculum examination with a 6-hour interval. Fetal monitoring, PROM management, vaginal dinoprostone administration and/or induction with amniotomy and oxytocin were managed following the same protocols of study participants. 
OutcomesWomen: vaginal delivery not achieved within 24 hours, CS.
Fetal/infant: Apgar score < 7 at 5 minutes. 
NotesMulticentre/single centre: multi-centre (it was conducted in 2 hospitals).
Setting: Italy.
Additional outcomes reported: Induction-to-delivery time, rate of CS for fetal distress, incidence of uterine hyperstimulation, incidence of umbilical artery pH < 7.01, rate of vaginal gel required as a second-line induction procedure, suspicious/ominous CTS in labour, stained amniotic fluid, atypical vaginal bleeding, oxytocin before labour, oxytocin in labour, blood loss at delivery, blood loss after vaginal delivery. 
Allocation concealmentC - Inadequate 
StudyThiery 1984 
MethodsRandomisation: RCT. Method of generation of the allocation sequence unclear.
Allocation concealment: unclear.
Blinding: 'double blind'.
Follow up: no loss of participants reported. 
Participants121 women were enrolled, 40 in gel group, 41 in tablet group and 40 in control group.
Eligibility: between the ages of 16-35 years, in good health, having a normal pregnancy at term (38-42 weeks' gestation), with a singleton fetus in vertex presentation, an intact uterus, no contraindications for labour induction and vaginal delivery, not in labour, intact membranes, Bishop score (4) of 5 or less, and no contraindications for treatment with prostaglandins.
Exclusion: no information provided. 
InterventionsGel group: IC gel PGE2 0.5 mg and intravaginal placebo tablets.
Tablet group: IC placebo gel and intravaginal tablets 2 mg PGE2.
Control group: IC placebo gel and intravaginal placebo tablets.
If the cervix was ripe (Bishop score more than 6) after a 12 hour observation period, labour induction was started by conventional methods (low amniotomy +/- intravenous oxytocin). 
OutcomesWomen: CS, cervix unfavourable/unchanged after 12 hours, vomiting, diarrhea, uterine hyperstimulation with FHR changes, PPH.
Fetal/infant: Apgar score < 7 at 5 minutes. 
NotesMulticentre/single centre: single centre.
Setting: Belgium.
Additional outcomes reported: labour within 12 hours after treatment, mean changes in Bishop score in 12 hours, more than 1 softening procedure before delivery, mean treatment delivery interval, softening efficacy stratified by admission Bishop score, gastrointestinal upset, uterine contractile abnormality, FHR abnormalities, Apgar score < 7 at 1 minute, FHR patterns, laboratory assays (liver enzymes, alkaline phosphatase, uric acid, creatinine, complete blood count, urinalysis, scalp pH and umbilical artery blood pH). 
Allocation concealmentB - Unclear 
StudyTrofatter 1985 
MethodsRandomisation: RCT. Method of generation of the allocation sequence unclear.
Allocation concealment: unclear.
Blinding: both participants and therapist were blinded to the study group.
Follow up: no loss of participants reported. 
Participants59 women were enrolled, 30 in experimental group and 29 in control group.
Eligibility: medical or obstetric indications for induction of labour, Bishop score 4 or less, a reactive nonstress test or a negative contraction stress test.
Exclusion: hypersensitivity to prostaglandins, history of asthma, glaucoma, elevated intraocular pressure, vaginal bleeding, ruptured membranes, previous CS, previous attempt at induction of labour. 
InterventionsExperimental: IC gel PGE2 0.5 mg.
Control: no treatment. Participants had the sterile cathether inserted into the cervix but received no gel.
Both groups had oxytocin after 12 hours if not in labour. Any participants who subsequently developed uterine contractions was managed and monitored as appropriate for her care in labour. 
OutcomesWomen: CS, uterine hyperstimulation with FHR changes, instrumental vaginal delivery.
Fetal/infant: no outcomes reported. 
NotesMulticentre/single centre: multi-centre
Supported by The Upjohn Company, Kalamazoo, Michigan.
Setting: USA.
Additional outcomes reported: Bishop score, time until complete dilatation, induction-to-delivery interval, rupture of membranes-to-delivery interval, labour prior to oxytocin, delivery prior to oxytocin, spontaneous delivery, estimated loss of blood, birthweight, Apgar score at 1 and 5 minutes, cord arterial pH. 
Allocation concealmentB - Unclear 
StudyTrofatter 1993 
MethodsRandomisation: RCT. Method of generation of the allocation sequence unclear.
Allocation concealment: unclear.
Blinding: open study.
Follow up: 26 (13 in each group) were excluded. 
Participants514 women were enrolled, 265 in experimental group and 249 in control group.
Eligibility: a pregnancy at or near term, medically indicated inductions, unfavourable cervix (BS < 5).
Exclusion: no information provided. 
InterventionsExperimental: 0.5 mg of dinoprostone cervical gel by endocervical administration.
Control: no treatment.
Both groups had oxytocin after 12 hours if not in labour. 
OutcomesWomen: CS, gastrointestinal side-effects, hyperstimulation with and without FHR changes, uterine rupture.
Fetal/infant: Apgar score < 7 at 5 minutes.

Lucas 1986 - Oxytocin augmentation: 22/27 in PGE2 group and 23/23 placebo group. 
NotesMulticentre/single centre: multi-centre.
Setting: USA.
Additional outcomes: Bishop score after 12 hours from treatment, initiation of labour, induction-delivery interval, side-effects, fever, abnormal FHR, Apgar score < 7 at 1 minute.
Some individual centres (Lucas 1986 and Yonekura 1985) published their own data. These data have not been entered into the meta-analysis, as they are already reported in the Trofatter 1993 paper which is the full multi-centre trial report. However, one of the centres ( Lucas 1986) published additional data. These additional data have not been entered into Review Manager, but are presented in this table (outcomes) and in the text of the review (Description of studies). 
Allocation concealmentB - Unclear 
StudyTroostwijk 1992 
MethodsRandomisation: RCT. Computer-generated allocation sequence.
Allocation concealment: coded identical preparation was kept by the pharmacist.
Blinding: 'double blind'.
Follow up: 1 women in experimental group was not included in the evaluation because of emergency CS. 
Participants139 women were enrolled, 71 in experimental group and 68 in placebo group.
Eligibility: a gestational age of more than 36 weeks, an unripe cervix (BS < 6) and intact membranes, a medical or obstetric indication for induction of labour or a justified elective induction.
Exclusion: more or less regular uterine contractions, an unavailing previous attempt at the induction of labour, multiple gestation, breech presentation, fetal growth retardation with an estimated birthweight below 2500 g, suspected fetal distress, intrauterine fetal death, and contraindications to the use of preparation (such as hypersensitivity to prostaglandins, a history of asthma or glaucoma, previous CS or other uterine surgery, and uterine bleeding of uncertain etiology). 
InterventionsExperimental: IC gel PGE2 0.5 mg.
Control: IC placebo gel.
After the following 9-hour study period and disclosure of the code, participants who received the placebo-preparation, could get a subsequent treatment with active preparation. 
OutcomesWomen: CS, uterine hyperstimulation without FHR changes, instrumental vaginal delivery, maternal side-effects.
Fetal/infant: Apgar score < 7 at 5 minutes. 
NotesMulticentre/single centre: multi-centre.
Setting: Netherlands.
Additional outcomes reported: successful cervical ripening, spontaneous delivery, birthweight, pH of the umbilical cord blood. 
Allocation concealmentA - Adequate 
StudyUlmsten 1982 
MethodsRandomisation: this trial included 2 parts, so only the information about the RCT part is included in this table. Method of generation of the allocation sequence was unclear.
Allocation concealment: unclear.
Blinding: 'double blind'.
Follow up: no loss of participants reported. 
Participants50 women were enrolled in the RCT, 25 in experimental group and 25 in control group.
Eligibility: nulliparas women with an unfavourable cervical state at term, labour requiring to be induced for medical or strong psychosocial reasons.
Exclusion: breech presentation, multiple pregnancy, or low-implanted placenta. 
InterventionsExperimental: IC gel PGE2 0.5 mg.
Control: IC gel placebo.
From 15 to 30 minutes before to 1 hour after gel application, participants were monitored by external cardiotocography. Participants in whom no abnormalities were registered and labour failed to be induced were referred to the antenatal care unit of the department. Those in whom labour was established were supervised according to the routine of the department, which included external or internal cardiotocography; scalp blood samples were taken when indicated. Amniotomy was not performed until the cervix was dilated 4 cm or more and labour was well established. Oxytocin or other stimulating agents were not infused. 
OutcomesWomen: vaginal delivery not achieved within 24 hours, CS.
Fetal/infant: Apgar score < 7 at 5 minutes. 
NotesMulticentre/single centre: multi-centre.
Setting: Sweden.
Additional outcomes: cervical score after treatment. 
Allocation concealmentB - Unclear 
StudyUlmsten 1985 
MethodsRandomisation: RCT. Method of generation of the allocation sequence unclear.
Allocation concealment: unclear.
Blinding: for 58 nulliparous women, 'double blind' was employed in this study; for 25 participants of mixed parity, it was open.
Follow up: no loss of participants reported. 
Participants83 women were enrolled, among which 19 in IC PGE2 gel group (blind study), 19 in intravaginal PGE2 group (blind study), 20 in placebo group (blind study) and 25 in IC PGE2 gel group (open study).
Eligibility:
For blind study: pregnant women at term, nulliparous, unfavourable cervical scores (Bishop score of 5 or less).
For open study: women of mixed parity and unfavourable cervical scores (Bishop score of 5 or less).
Exclusion: no information provided. 
InterventionsExperimental: IC PGE2 gel 0.5 mg + an inactive suppository.
Control: a suppository containing 2 mg PGE2 + IC inactive gel.
An amniotomy was never done until labour was well established and the cervix at least 4 cm dilated. Participants not in labour but with a favourable cervical score 24 hours after the start of the treatment were induced by an IV oxytocin infusion. The infusion started with a dose of 2 mu/minute. It was subsequently increased with 2 mu every 30 minutes until labour was well established. The maximum dose infused was not allowed to exceed 24 mu/minutes. If the cervix was still unfavourable 24 hours from start of treatment, the participant was given IC PGE2 gel. 
OutcomesWomen: vaginal delivery not achieved within 24 hours, CS.
Fetal/infant: Apgar score < 7 at 5 minutes. 
NotesMulticentre/single centre: single centre.
Setting: Sweden.
Additional outcomes reported: cervical score after 16-20 hours after treatment, increased myometrial activity, maternal gastrointestinal discomfort, hyperpyrexia, signs of infection, children's health at 1 week and at 6 months. 
Allocation concealmentB - Unclear 
StudyWieland 1999 
MethodsRandomisation: RCT. Generation of the allocation sequence by shuffling cards.
Allocation concealment: opaque sealed sequentially numbered envelopes.
Blinding: no information provided.
Follow up: 9 were excluded for protocol violations. 
Participants78 women were enrolled, 35 in the IC group, 34 in the intravaginal group and 9 excluded.
Eligibility: term gestation, cephalic presentation, Bishop score < 5, reactive nonstress test or negative oxytocin challenge test, and approval for vaginal delivery.
Exclusion: previous uterine surgery or presented with a history of ruptured membranes. 
InterventionsIC group: IC gel PGE2 l 0.5 mg. Dosing was repeated every 4 to 6 hours for a total of up to 3 doses during the course of the night.
Intravaginal group: intravaginal PGE2 10 mg insert, removed 12 hours later.
In the case of hyperstimulation or tachysystole, the insert was removed; if the gel was used, terbutaline was administered subcutaneously. 
OutcomesWomen: CS, instrumental delivery, uterine hyperstimulation with FHR changes, uterine hyperstimulation without FHR changes.
Fetal/infant: no outcomes reported. 
NotesMulticentre/single centre: single centre.
Setting: USA.
Additional outcomes reported: change in Bishop score, change in Bishop score at least 3 points, labour without oxytocin, time interval from admission to delivery, failed induction, spontaneous vaginal delivery, cost. 
Allocation concealmentA - Adequate 
StudyWingerup 1978 
MethodsRandomisation: RCT. Method of generation of the allocation sequence unclear.
Allocation concealment: unclear.
Blinding: unclear.
Follow up: no loss of participants reported. 
Participants20 women were enrolled, 10 in experimental group and 10 in control group.
Eligibility: pregnancy at term, unfavourable cervical state (modified Bishop score not great than 5), nulliparae, vertex presentation, intact membranes.
Exclusion: low implanted placentas. 
InterventionsExperimental: IC gel PGE2 1 mg.
Control: IC placebo gel. 
OutcomesWomen: CS, instrumental delivery, uterine hyperstimulation with FHR changes, uterine hyperstimulation without FHR changes, maternal side-effects, epidural analgesia.
Fetal/infant: Apgar score < 7 at 5 minutes. 
NotesMulticentre/single centre: single centre.
Setting: Sweden.
Additional outcomes reported: vaginal delivery, change in Bishop score.
Also report outcomes for 41 women not randomised. 
Allocation concealmentA - Adequate 
StudyYuen 1996 
MethodsRandomisation: RCT. Computer-generated allocation sequence.
Allocation concealment: sealed opaque envelopes.
Blinding: no information provided.
Follow up: 5 were excluded for protocol violations. 
Participants119 women were enrolled, 38 in group A, 41 in group B and 40 in group C.
Eligibility: requiring induction of labour, a singleton pregnancy in a vertex presentation, a cervical Bishop score of 4 or less.
Exclusion: ruptured membranes, 2 or more previous CS, regular uterine contractions and conditions necessitating immediately delivery. 
InterventionsGroup A: insertion of the Atad Ripener Device.
Group B: IC insertion of 0.5 mg PGE2 gel.
Group C: intravaginal placement of 3 mg of PGE2 pessary. Repeated 6 hours later if the cervix remained unfavourable (Bishop score < 6) and there were no significant uterine contractions.
In all 3 groups, if the Bishop score was 6 or above, induction of labour was carried out by rupturing the membranes and/or intravenous administration of oxytocin. 
OutcomesWomen: CS, uterine hyperstimulation with FHR changes, instrumental delivery, uterine hyperstimulation without FHR changes.
Fetal/infant: Apgar score < 7 at 5 minutes. 
NotesMulticentre/single centre: single centre.
Setting: Hong Kong.
Additional outcomes reported: complications during the ripening period, successful cervical ripening, Bishop score change, vaginal delivery, duration of labour, postdelivery uterine atony, birthweight, Apgar score < 7 at 1 minute. 
Allocation concealmentA - Adequate 
StudyZanini 1989 
MethodsRandomisation: RCT. Allocation sequence from a table of numbers.
Allocation concealment: unclear.
Blinding: no information provided.
Follow up: 6 were excluded for protocol violations. 
Participants106 women were enrolled, 52 in the IC group, 48 in the intravaginal group and 6 excluded.
Eligibility: singleton pregnancy, vertex presentation, intact membranes, Bishop score less than 6, and gestational age more than 35 weeks.
Exclusion: a history of asthma, glaucoma, previous CS delivery, uterine surgery, second- or third-trimester haemorrhage, or parity above 5. 
InterventionsIC group: IC gel PGE2 0.5 mg.
Intravaginal group: intravaginal gel PGE2 3 mg.
If the Bishop score was greater than 5, labour was induced by artificial rupture of membranes, followed by intravenous oxytocin 2 hours later if necessary. If the Bishop score was 5 or less, the gel was reapplied for a total of 3 times, alternating the route of administration. 
OutcomesWomen: CS, uterine hyperstimulation with FHR changes, uterine hyperstimulation without FHR changes, instrumental delivery, maternal side-effects, nausea, vomiting, diarrhoea.
Fetal/infant: no outcomes reported. 
NotesMulticentre/single centre: single centre.
Setting: Italy.
Additional outcomes reported: Bishop score change, maternal fever, spontaneous vaginal delivery. 
Allocation concealmentB - Unclear 

BS: Bishop score
CS: caesarean section
CST: contraction stress test
CTG: cardiotocography
FHR: fetal heart rate
HELLP: hemolysis, elevated liver enzymes, low platelets
IC: intracervical
ICPG: intracervical prostaglandin
ITT: intention to treat
IV: intravenous
LSCS: low-segment CS
NICU: neonatal intensive care unit
NST: nonstress test
PG: prostaglandin
PPH: postpartum haemorrhage
PROM: premature rupture of the membranes
RCT: randomised controlled trial
VD: vaginal delivery



Characteristics of excluded studies

StudyReason for exclusion
Aggarwal 2006 Comparing vaginal misoprostol with intracervical prostaglandin. 
Bredow 1993 Not an RCT. 
Cararach 1994 Trial assessing 3 types of management of premature rupture of membranes of 34 weeks or more, therefore excluded. Women randomised to either induction of labour at 12 hours of PROM, PGE2 0.5 mg intracervical gel or expectant management until 48 hours of PROM. 
D'Aniello 2003 Women were 'consecutively enrolled' into the study. 
Egarter 1988 Method of randomisation not described and inconsistencies in data. We tried to contact the author but have been unsuccessful. 
Ekblad 1994 Inadequate method of randomisation (alternation). In addition, results were unclearly reported. 
Facchinetti 2005 Women received either 0.5 mg intracervical dinoprostone gel, or 10 mg vaginal dinoprostone insert. After 6 hours, women (in either group) with a Bishop score of less than 4 received another dose of gel, while those with Bishop scores between 4 and 6 received 2 mg dinoprostone gel by the vaginal route. After 12 hours, the vaginal insert was removed. After 24 hours of treatment, 2 mg dinoprostone administered to women in both groups who were not experiencing regular uterine contractions. 6 hours later, every woman who was not in labour had her labour induced with an oxytocin infusion. Amniotomy was performed only in women in labour with at least 5 cm of cervical dilatation. Oxytocin augmentation was done in the second stage of labour if necessary. Trial does not meet eligibility criteria of review. 
Fuchs 1984 Not clear if an RCT. Compared endocervical PGE2 with extra-amniotic PGE2. 
Garcia 1988 Report does not state if trial randomised, gestation of women, or give any numerical data. 
Gittens 1996 Comparison of intracervical prostaglandin for induction versus expectant management. 
Goeschen 1985 Not clear if a randomised controlled trial. Also both groups received prostaglandin gel. 
Gonen 1994 Comparison of intracervical prostaglandin, followed by oxytocin after 6 hours, for induction of labour versus expectant management, followed by oxytocin after 24 hours, in women with PROM. 
Hennessey 1998 Comparison of 0.5 mg intracervical gel (Prepidil) with oxytocin administered 30 minutes after instillation or 10 mg sustained-release vaginal insert (Cervidil). 
Henson 1987 Women recruited in preterm pregnancy. 
Herabutya 1992 Comparison of intracervical prostaglandin for induction versus expectant management. 
Herabutya 1993 Comparison of intracervical to intravaginal PGE2. In protocol, any participant requiring more than 1 dose of either preparation or those sent home who then returned in spontaneous labour were excluded. 
Iftikhar 1991 No outcome data reported. 126 women randomised. 63 women allocated to 0.5 mg intracervical gel 2 doses and 63 women to intravaginal pessary 2 mg doses. Unable to locate authors to obtain data (05/04/07). 
Ingemarsson 1991 Abstract only and data not presented, R Smyth contacted I Ingemarsson for additional information. 
Kamat 2002 Doesn't appear to be an RCT. report states 'the cases were divided into 2 groups' . Unable to locate authors to obtain verification (23/04/07). 
Kaminski 1994 Trial compares intracervical PGE2 with oxytocin IV. 
Kupietz 1994 Trial compares intracervical PGE2 0.5 mg administered in the morning compared with at night. 
Lotshaw 1994 All women received intracervical PGE gel 0.5 mg either 6 hour or 1 hour prior to administration of oxytocin. 
Luther 1983 Comparison of synthetic to natural prostaglandin E2. Same dose in both arms (0.5 mg). 
Lyndrup 1992 Presentation of data from 4 prospective, randomised trials: 2 of which compared vaginal PGE2 with oxytocin. 
Mackenzie 1988 Prostaglandin administered vaginally, not intracervically. 
Megalo 1998 Trial comparing vaginal misoprostol to intracervical followed by intravaginal PGE2. 
Minaretzis 1993 During a first period all women were allocated to IC PGE2 0.5 mg (40 women), during a second period to IC PGE2 1.5 mg (35 women), then to 2.5 mg (35 women). Despite blinding of clinicians and the fact that women were included consecutively, this method was considered as inappropriate. 
Mink 1994 Protocol of administration unclear. Method of randomisation and concealment of allocation unclear. Results reported unclearly. 
Muller 1995 Comparison of IC PGE2 0.5 mg and intravaginal PGE2 tablets 3 mg. Exclusion because of inadequate method of randomisation and concealment of allocation. 
Muller 2000 Comparison of IC PGE2 0.5 mg and intravaginal PGE2 tablets 3 mg. Exclusion because of a large number of exclusions: 302 women included, 176 reported (62 in the IC group and 102 in the IV group). 
Noah 1985 Comparison of 2 doses 0.25 mg 6-hourly to 1 dose 0.5 mg PGE2 (followed 6 hours later by a dose of placebo). 
Nuutila 1997 Focus of this trial was fetal doppler flow, but possible that authors collected data relevant to this review, therefore R Smyth emailed M Nuutila (10/04/07) and O Ylikorkala (23/04/07) for additional data - no response received (27/04/07). 
Parewijck 1987 Unpublished trial. Authors have been written to - no response. 
Paul 1988 Comparison of intracervical prostaglandin for induction versus expectant management. 
Penna 1991 Complex trial design with varying dose in each arm dependent on bishops score. If Bishops score > 7 in either arm then participants underwent ARM and oxytocin alone. Data not divided according to dose allocation. 
Polvi 1994 Focus of trial doppler flow, but possible that authors collected data relevant to this review, therefore R Smyth emailed JP Pirhonen and JP Pirhonen (24/04/07) for data - no response. 
Rath 1985 Comparison of different dosages of PGE2 intracervical gel (25, 50, 100 micrograms). 
Rayburn 1988 Unclear wether intervention was intracervical or vaginal. High dose (2.5 mg) more compatible with intravaginal use. 
Rayburn 1999 Comparison of IC 0.5 mg prostaglandin for induction versus expectant management. 
Reichel 1985 Trial reports lab data only. 
Roberts 1986 Prostaglandin administration on the external cervix. Dose more likely to be compatible with intravaginal administration than intracervical (3 mg). 
Sahraoui 2005 Comparing PGE2 gel with expectant management. 
Sanchez-Ramos 1995 Comparison of commercial with compounded prostaglandin E2. Same dose in both arms (0.5 mg). 
Schneider 1994 Not clear if a randomised trial as all women with medium to ripe cervix received vaginal tablets and all women with unripe cervix received cervical gel. Also 13% of women recruited with less than or up to 37 weeks' gestation, and 47% postrandomisation exclusions based on data errors. 
Shaala 1989 Mode of induction involved direct injection of prostaglandin into the body of the cervix. 
Skajaa 1991 Comparison of solid with liquid prostaglandin E2. Same dose in both arms (0.5 mg). 
Tey 1995 Comparison of induction with intracervical prostaglandin versus expectant management for fetuses with suspected macrosomia. 
Voss 1996 Comparison of varying doses of intracervical prostaglandins. Numerous postrandomisation exclusions. (only 229 of original 291 participants analysed) 
Webb 1997 No denominator data given. 
Williams 1985 PGE2 3 mg and 5 mg administered "onto the portio vaginalis of the cervix". Probably comparison of vaginal PG and placebo. 
Wyldes 1992 Mike Wyldes confirmed that trial never commenced (26/04/07). 
Yacoob 1993 Comparison of 0.5 mg intracervical PGE2 gel compared with 0.5 mg 0.5 mg oral tablet. 
van Dessel 1991 Women were already in early labour. 

ARM:
IC: intracervical
PROM: premature rupture of membranes
RCT: randomised controlled trial



TABLAS ADICIONALES

Table 01 Methodological quality of trials
Methodological itemAdequateInadequate
Generation of random sequence. Computer-generated sequence, random-number tables, lot drawing, coin tossing, shuffling cards, throwing dice. Case number, date of birth, date of admission, alternation. 
Concealment of allocation. Central randomisation, coded drug boxes, sequentially sealed opaque envelopes. Open allocation sequence, any procedure based on inadequate generation. 


REFERENCIAS
Referencias de los estudios incluidos en esta revisión

Bernstein 1991{Solo datos publicados}
Bernstein EP. Prostaglandin E2 gel for cervical ripening and labour induction. A Canadian multi-centre placebo-controlled trial. Proceedings of the Annual Meeting of Society of Obstetricians and Gynaecologists of Canada; 1991 June 11-15; Toronto, Ontario, Canada. 1991:70.

Bernstein EP, Leyland N, Gurland P, Gare D. Effect of administration of PGE2 gel and placebo gel into the cervical canal on cervical softening and induction of labour. Proceedings of the Annual Meeting of Society of Obstetricans and Gynaecologists of Canada. 1986:108.

*Bernstein P. Prostaglandin E2 gel for cervical ripening and labour induction: a multicentre placebo-controlled trial [published erratum appears in Can Med Assoc J 1992 Apr 15;146(8):1290]. Canadian Medical Association Journal 1991;145:1249-54.

Bernstein P, Leyland N, Gurland P, Gare D. Cervical ripening and labor induction with prostaglandin E2 gel: a placebo-controlled study. American Journal of Obstetrics and Gynecology 1987;156:336-40.

Christilaw J, King JF. A randomised, placebo controlled trial to determine the effect of intracervical prostaglandin gel on the unripe cervix, prior to induction of labour. Proceedings of the Annual Meeting of Society of Obstetricians and Gynaecologists of Canada; 1986. 1986:107.

Buttino 1990{Solo datos publicados}
Buttino LT, Garite TJ. Intracervical prostaglandin in postdate pregnancy. A randomized trial. Journal of Reproductive Medicine 1990;35:155-8.

Cabrol 1988{Solo datos publicados}
Cabrol D, Bernard N, Chouraqui A, Domenichini Y, Lemaire P, Lopes P, et al. Ripening of the cervix uteri at term by a single intracervical application of prostaglandin E2 gel. Journal de Gynecologie, Obstetrique et Biologie de la Reproduction 1988;17:527-34.

Chyu 1997{Solo datos publicados}
Chyu JK, Strassner HT. Prostaglandin E2 for cervical ripening: a randomized comparison of Cervidil versus Prepidil. American Journal of Obstetrics and Gynecology 1997;177:606-11.

Corrado 2001{Solo datos publicados}
Corrado F, Cannata ML, Facciola G, Stella NC. Intravaginal vs. intracervical pge2 gel first application for labor induction. International Journal of Gynecology & Obstetrics 2001;75:195-7.

Darroca 1996{Solo datos publicados}
Darroca RJ, Buttino L, Miller J, Khamis HJ. Prostaglandin E2 gel for cervical ripening in patients with an indication for delivery. Obstetrics & Gynecology 1996;87:228-30.

Duhl 1997{Solo datos publicados}
Duhl A, Tolosa J, Leiva M, Memiroff R. Randomized trial of intravaginal gel, intravaginal time release insert and intracervical gel with prostaglandin E2 for induction of labour. American Journal of Obstetrics and Gynecology 1997;176(1 Pt 2):S113.

Ekman 1983{Solo datos publicados}
Ekman G, Forman A, Marsal K, Ulmsten U. Intravaginal versus intracervical application of prostaglandin E2 in viscous gel for cervical priming and induction of labor at term in patients with an unfavorable cervical state. American Journal of Obstetrics and Gynecology 1983;147:657-61.

El-Din 2000{Solo datos publicados}
El-Din NMN, El-Morghatz DAM. Cervical ripening and induction of labour with misoprostol, prostaglandin E2 or prostaglandin E2 gel: a randomized comparative clinical trial. XVI FIGO World Congress of Obstetrics and Gynecology (Book 4); 2000 Sept 3-8; Washington DC, USA. 2000:29.

Gilson 1993{Solo datos publicados}
Gilson GJ, Curet LB. Intracervical dinoprostone (PGE2): does it actually lower the cesarean section rate. American Journal of Obstetrics and Gynecology 1991;164:405.

*Gilson GJ, Izquierdo LA, Chatterjee MS, Curet LB, Qualls CR. Prevention of caesarean section. Does intracervical dinoprostone work?. Western Journal of Medicine 1993;159:149-52.

Grünberger 1986{Solo datos publicados}
Grünberger W, Spona J. The effect of paracervical PGE2 instillation on levels of maternal serum 13,14-dihydro-15-keto-PGF2alpha and progesterone. Archives of Gynecology 1986;239:93-9.

Hales 1994{Solo datos publicados}
Hales K, Rayburn W, Turnbull G, Christensen D, Patatanian E. Double-blind comparison of intracervical and intravaginal prostaglandin E2 for cervical ripening and induction of labor. American Journal of Obstetrics and Gynecology 1994;170:365.

*Hales KA, Rayburn WF, Turnbull GL, Christensen HD, Patatanian E. Double-blind comparison of intracervical and intravaginal prostaglandin E2 for cervical ripening and induction of labor. American Journal of Obstetrics and Gynecology 1994;171:1087-91.

Heinzl 1980{Solo datos publicados}
Heinzl S, Ramzin MS, Schneider M, Luescher KP. Priming of cervix with prostaglandin gel during immature birth situation at term (author's transl). Zeitschrift fur Geburtshilfe und Perinatologie 1980;184:395-400.

Hidar 2000{Solo datos publicados}
Hidar S, Bibi M, Jerbi M, Bouguizene S, Nouira M, Mellouli R, et al. Contribution of intracervical PGE2 administration in premature rupture of the membranes at term. Prospective randomised clinical trial. Journal de Gynecologie, Obstetrique et Biologie de la Reproduction 2000;29:607-13.

Hutchon 1980{Solo datos publicados}
*Hutchon DJ, Geirsson R, Patel NB. A double-blind controlled trial of PGE2 gel in cervical ripening. International Journal of Gynecology & Obstetrics 1980;17:604-7.

Hutchon DJR, Geirsson RT, Patel NB. A double-blind controlled trial of intracervical prostaglandin E2 in cervical ripening [abstract]. Acta Obstetricia et Gynecologica Scandinavica 1980;59(Suppl 93):83.

Irion 1998{Solo datos publicados}
*Irion O, Pedrazzoli J, Mermillod B. A randomized trial comparing vaginal and cervical prostaglandin gel for cervical ripening and labor induction. Obstetrics & Gynecology 1998;91:65-71.

Pedrazzoli J, Irion O, Mermillod B, Beguin F. A randomised comparison of an intravaginal and an intracervical prostaglandin E2 gel for cervical ripening and induction of labor. American Journal of Obstetrics and Gynecology 1997;176:S111.

Pedrazzoli J, Irion O, Mermillod B, Beguin F. A randomised comparison of an intravaginal and an intracervical prostaglandin E2 gel for cervical ripening and induction of labour. 20th Congress of the Swiss Society of Gynecology and Obstetrics; 1997 June; Lugano, Switzerland. 1997:10.

Keirse 1995{Solo datos publicados}
de Koning Gans GHJ, Keirse MJNC. A comparison between intra-cervical and intra-vaginal application of prepidil gel for the induction of labour. Personal communication. 1995.

*Keirse MJ, de Koning Gans HJ. Randomized comparison of the effects of endocervical and vaginal prostaglandin E2 gel in women with various degrees of cervical ripeness. Dutch Collaborative Prostaglandin Trialists' Group. American Journal of Obstetrics and Gynecology 1995;173:1859-64.

Keirse MJNC, Schulpen MAGT, De Koning Gans HJ. A randomized controlled comparison of endocervical and vaginal PGE2 in triacetin gel for cervical ripening and induction of labour. Proceedings of 2nd European Congress on Prostaglandins in Reproduction; 1991 April 30-May 3; The Hague, Netherlands. 1991:214.

Kemp 2000{Solo datos publicados}
Kemp B, Winkler M, Rath W. Induction of labor by prostaglandin E2 in relation to Bishop score. International Journal of Gynecology & Obstetrics 2000;71:13-7.

Larmon 2002{Solo datos publicados}
Larmon JE, Magann EF, Dickerson GA, Morrison JC. Outpatient cervical ripening with prostaglandin E2 and estriol. Journal of Maternal-Fetal and Neonatal Medicine 2002;11:113-7.

Laube 1986{Solo datos publicados}
Laube DW, Zlatnik FJ, Pitkin RM. Preinduction cervical ripening with prostaglandin E2 intracervical gel. Obstetrics & Gynecology 1986;68:54-7.

Legarth 1988{Solo datos publicados}
*Legarth J, Guldbaek E, Scher NJ. The efficiency of prostaglandin E2 vaginal suppositories versus intracervical prostaglandin gel for induction of labor in patients with unfavorable inducibility prospects. European Journal of Obstetrics & Gynecology and Reproductive Biology 1988;27:93-8.

Legarth J, Guldbaek E, Secher NJ. The efficiency of prostaglandin E2 vaginal suppository vs intracervical prostaglandin gel for induction of labor in patients with unfavorable Bishop score. Archives of Gynecology 1985;237(Suppl 1):103.

Lien 1998{Solo datos publicados}
Lien JM, Morgan MA, Garite TJ, Kennedy KA, Sassoon DA, Freeman RK. Antepartum cervical ripening: applying prostaglandin E2 gel in conjunction with scheduled nonstress tests in postdate pregnancies. American Journal of Obstetrics and Gynecology 1998;179:453-8.

Lopes 1991{Solo datos publicados}
*Lopes P, Besse O, Sagot P, Dantal F, de Morel P, Panel N, et al. The value of the administration of prostaglandin E2 on the biodegradable support of the maturation of the cervix uteri and the induction of labor. Journal de Gynecologie, Obstetrique et Biologie de la Reproduction 1991;20:827-32.

Lopes P, Besse O, Sagot P, Dantal F, De Morel P, Panel N, et al. Induction of labour with vaginal prostaglandin E2 with a 'Spongel'. Results of a prospective randomised study taking into account Bishops score and the dose of PGE2 used. Journal de Gynecologie, Obstetrique et Biologie de la Reproduction 1990;19:505.

Lopes P, Besse O, Sagot P, Dantal F, De Morel P, Panel N, et al. PGE2 application on a biodegradable support for cervix ripening and induction of labour. Proceedings of 2nd European Congress on Prostaglandins in Reproduction; 1991 April 30-May 3; The Hague, Netherlands. 1991:147.

Lyndrup 1991{Solo datos publicados}
Lyndrup J. Induction of labor by PGE2 and other local methods. Physiology, methods and guidelines for patient selection. Acta Obstetricia et Gynecologica Scandinavica 1996;75:86-7.

*Lyndrup J, Nickelsen C, Guldbaek E, Weber T. Induction of labor by prostaglandin E2: intracervical gel or vaginal pessaries?. European Journal of Obstetrics & Gynecology and Reproductive Biology 1991;42:101-9.

Lyndrup J, Nickelsen C, Guldbaek E, Weber T. Induction of labour by prostaglandin-E2: intracervical gel or vaginal pessaries?. Proceedings of 13th World Congress of Gynaecology and Obstetrics (FIGO); 1991 Sept 15-20; Singapore. 1991:70.

McKenna 1999{Solo datos publicados}
McKenna DS, Costa SW, Samuels P. Prostaglandin E2 cervical ripening without subsequent induction of labor. Obstetrics & Gynecology 1999;94:11-4.

Milliez 1993{Solo datos publicados}
Milliez JM, Jannet D, Touboul C, Khelifati Y, El Medjadji M. Two different regimens of preinduction ripening of the uterine cervix with prostaglandin E2: a randomized clinical study. European Journal of Obstetrics & Gynecology and Reproductive Biology 1993;50:163-8.

Nager 1987{Solo datos publicados}
Nager CW, Key TC, Moore TR. Cervical ripening and labor outcome with preinduction intracervical prostaglandin E2 (Prepidil) gel. Journal of Perinatology 1987;7:189-93.

NICHHD 1994{Solo datos publicados}
Medearis AL. Postterm pregnancy: active labour induction (PGE2 gel) not associated with improved outcomes compared to expectant management. A preliminary report. Proceedings of 10th Annual Meeting of Society of Perinatal Obstetricians; 1990 Jan 23-27; Houston, Texas, USA. 1990:17.

*The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. A clinical trial of induction of labor versus expectant management in postterm pregnancy. American Journal of Obstetrics and Gynecology 1994;170:716-23.

Nimrod 1984{Solo datos publicados}
Nimrod C, Currie J, Yee J, Dodd G, Persaud D. Cervical ripening and labor induction with intracervical triacetin base prostaglandin E2 gel: a placebo-controlled study. Obstetrics & Gynecology 1984;64:476-9.

Noah 1987{Solo datos publicados}
Bung P, Baer S, Djahanschahi D, Huch R, Huch A, Huber JF, et al. Multicenter experiences with the intracervical administration of a new PGE2 gel in labor induction. Geburtshilfe und Frauenheilkunde 1986;46:93-7.

Keirse MJNC, Kanhai HHH, Verwey RA. European multi-centre trial of intracervical PGE2 in triacetin gel: report of the Leiden data. In: Wood C, editor(s). The role of prostaglandins in labour. London: RSM Services Limited, 1985:93-100.

Keirse MJNC, Schulpen MAGT, Corbeij RSACM, Oosterbaan HP. Vaginal PGE2 gel vs intravenous oxytocin after cervical ripening with endocervical PGE2 gel. In: Keirse MJNC, de Koning Gans HJ, editor(s). Priming and induction of labour by prostaglandins "A state of the art". Leiden: Postgrad Med Ed Committee, 1987:53-76.

Kieback DG, Zahradnik HP, Quaas L, Kroner-Fehmel EE, Lippert TH. Clinical evaluation of endocervical prostaglandin E2-triacetin-gel for preinduction cervical softening in pregnant women at term. Prostaglandins 1986;32:81-5.

Kimball FA, Ruppel PL, Noah ML, Decoster JM, De La Fuente P, Castillo JM, et al. The effect of endocervical PGE2-gel (Prepidil) gel on plasma levels of 13,14-dihydro-15-keto-PGE2 (PGEM) in women at term. Prostaglandins 1986;32:527-37.

Kristoffersen M, Sande HA, Sande OS. Ripening of the cervix with prostaglandin E2-gel. A randomized study with a new ready-to-use compound of triacetin-prostaglandin-E2-gel. International Journal of Gynecology & Obstetrics 1986;24:297-300.

*Noah ML, DeCoster JM, Fraser TJ, Orr JD. Preinduction cervical softening with endocervical PGE2 gel. A multi-center trial. Acta Obstetricia et Gynecologica Scandinavica 1987;66:3-7.

Pulle C, Granese D, Panama S, Celona A. Cervical ripening and induction of labour by single intracervical PGE2-gel application. Acta Therapeutica 1986;12:5-12.

Wiqvist I, Norstrom A, Wiqvist N. Induction of labor by intra-cervical PGE2 in viscous gel. Acta Obstetricia et Gynecologica Scandinavica 1986;65:485-92.

Zahradnik HP, Quaas L, Kroner-Fehmel EE, Kieback DG, Lippert TH. Cervix ripening using drugs before oxytocin labor induction. Clinical study of a new prostaglandin E2 triacetin gel. Geburtshilfe und Frauenheilkunde 1987;47:190-2.

Nuutila 1995{Solo datos publicados}
Nuutila M, Kajanoja P. Cervical ripening prior to labour induction with intracervical prostaglandin E2 gel in patients with preeclampsia. A placebo controlled study. Hypertension in Pregnancy 1995;14(3):313-7.

Nuutila 1996{Solo datos publicados}
Nuutila M, Kajanoja P. A randomized comparison of intravaginal and intracervical administration of prostaglandin E2 in cervical ripening. Acta Obstetricia et Gynecologica Scandinavica Supplement 1995;73:110-1.

*Nuutila M, Kajanoja P. Local administration of prostaglandin E2 for cervical ripening and labor induction: the appropriate route and dose. Acta Obstetricia et Gynecologica Scandinavica 1996;75:135-8.

Ottinger 1998{Solo datos publicados}
Ottinger WS, Menard MK, Brost BC. A randomized clinical trial of prostaglandin E2 intracervical gel and a slow release vaginal pessary for preinduction cervical ripening. American Journal of Obstetrics and Gynecology 1998;179:349-53.

Owen 1991{Solo datos publicados}
*Owen J, Winkler CL, Harris BA, Jr, Hauth JC, Smith MC. A randomized, double-blind trial of prostaglandin E2 gel for cervical ripening and meta-analysis. American Journal of Obstetrics and Gynecology 1991;165:991-6.

Owen J, Winkler CL, Hauth JC, Harris BA, Smith MC. A randomised double blind trial of prostaglandin E2 gel for cervical ripening and a meta analysis. American Journal of Obstetrics and Gynecology 1991;164:313.

Peccerillo 1995{Solo datos publicados}
Peccerillo JA, Egan JFX, Borgida A, Campbell WA. Comparison of intracervical PGE2 to intravaginal PGE2 for preinduction cervical ripening. American Journal of Obstetrics and Gynecology 1995;172:298.

Perez Picanol 1990{Solo datos publicados}
Perez Picanol E, Gamissans O, Lecumberri J, Jimenez M, Vernet M. Ripening the cervix with intracervical PGE2 gel in term pregnancies with premature rupture of membranes. Proceedings of 12th European Congress of Perinatal Medicine; 1990 Sept 11-14; Lyon, France. 1990:197.

Perry 2003{Solo datos publicados}
Perry MY, Leaphart WL. A randomized controlled trial using intracervical versus posterior fornix placement of dinoprostone. Obstetrics & Gynecology 2003;101(4):35S.

Perry MY, Leaphart WL. Randomized trial of intracervical versus posterior fornix dinoprostone for induction of labor. Obstetrics & Gynecology 2003;4:11S.

*Perry MY, Leaphart WL. Randomized trial of intracervical versus posterior fornix dinoprostone for induction of labor. Obstetrics & Gynecology 2004;103(1):13-7.

Poulsen 1991{Solo datos publicados}
Poulsen HK, Moller LK, Westergaard JG, Thomsen SG, Giersson RT, Arngrimsson R. Open randomized comparison of prostaglandin E2 given by intracervical gel or vagitory for preinduction cervical ripening and induction of labor. Acta Obstetricia et Gynecologica Scandinavica 1991;70:549-53.

Ramsey 2003{Solo datos publicados}
*Ramsey PS, Harris D, Ogburn PL, Heise RH, Magtibay PM, Ramin KD. Comparative efficacy and cost of the prostaglandin analogs dinoprostone and misoprostol as labour preinduction agents. American Journal of Obstetrics and Gynecology 2003;188(2):560-5.

Ramsey PS, Meyer L, Walkes BA, Harris D, Ogburn PL, Heise RH, et al. Cardiotocographic abnormalities associated with dinoprostone and misoprostol cervical ripening. Obstetrics & Gynecology 2005;105(1):85-90.

Rath 1999{Solo datos publicados}
Rath W, Heyl W, Kemp B. Intracervical versus intravaginal PGE2 gel for induction of labor. Perinatal Medizin 1998;10:81-3.

*Rath W, Kemp B, Heyl W. Prostaglandin E2 as a vaginal gel, intracervical gel or vaginal tablet for induction of labor: a prospective, randomized, multicenter trial. Geburtshilfe und Frauenheilkunde 1999;59:323-9.

Richardson 1991{Solo datos publicados}
Richardson CJ, Evans JF, Meisel RL. Duration of intracervical prostaglandin and caesarean section. American Journal of Obstetrics and Gynecology 1991;164:403.

Rix 1996{Solo datos publicados}
Møller M. Trial to assess the effects of cervical ripening and induction of labour by prostaglandin administration. Personal communication. 1991.

Rix P, Andersen K, Ladehoff P, Møller AM, Zdravkovic M. PGE2 vaginal tablets compared to ready prepared cervical PGE2 gel in ability to induce cervical ripening and labour by low Bishop scores. Proceedings of 1st European Congress on Prostaglandins in Reproduction; 1988 July 6-9; Vienna, Austria 1988. 1988:151.

*Rix P, Ladehoff P, Moller AM, Tilma KA, Zdravkovic M. Cervical ripening and induction of delivery by local administration of prostaglandin E2 gel or vaginal tablets is equally effective. Acta Obstetricia et Gynecologica Scandinavica 1996;75:45-7.

Seeras 1995{Solo datos publicados}
Seeras RC. Induction of labor utilizing vaginal vs. intracervical prostaglandin E2. International Journal of Gynecology & Obstetrics 1995;48:163-7.

Stempel 1997{Solo datos publicados}
Stempel JE, Prins RP, Dean S. Preinduction cervical ripening: a randomized prospective comparison of the efficacy and safety of intravaginal and intracervical prostaglandin E2 gel. American Journal of Obstetrics and Gynecology 1997;176:1305-9; discussion 1309-12.

Stiver 1991{Solo datos publicados}
Stiver KH, Davis MJ, Golichowski AM. Repeated intracervical prostaglandin administration for cervical ripening. American Journal of Obstetrics and Gynecology 1991;164:315.

Strobelt 2006{Solo datos publicados}
*Strobelt N, Meregalli V, Ratti M, Mariani S, Zani G, Morana S. Randomized study on removable PGE2 vaginal insert versus PGE2 cervical gel for cervical priming and labor induction in low-bishop-score pregnancy. Acta Obstetricia et Gynecologica Scandinavica 2006;85(3):302-5.

Strobelt N, Ratti M, Zani G, Meregalli V. Randomized study on two dinoprostone administration routes for cervical priming and labor induction in low bishop pregnancy. American Journal of Obstetrics and Gynecology 2003;189(6):S206.

Thiery 1984{Solo datos publicados}
Thiery M, Decoster JM, Parewijck W, Noah ML, Derom R, Van Kets H, et al. Endocervical prostaglandin E2 gel for preinduction cervical softening. Prostaglandins 1984;27:429-39.

Trofatter 1985{Solo datos publicados}
Trofatter KF, Bowers D, Gall SA, Killam AP. Preinduction cervical ripening with prostaglandin E2 (Prepidil) gel. American Journal of Obstetrics and Gynecology 1985;153:268-71.

Trofatter 1993{Datos publicados y no publicados}
Haas S, Lucas MJ. Impact of prepidil pre-induction cervical treatment. American Journal of Obstetrics and Gynecology 1993;168:361.

Lucas MJ, Leveno KJ, Williams ML, Brewster S. Efficacy of prostaglandin E2 gel in cervical ripening: preliminary results. Proceedings of 6th Annual Meeting of the Society of Perinatal Obstetricians; 1986 Jan 30-Feb 1; San Antonio, Texas, USA. 1986:240-56.

*Trofatter KF. Effect of preinduction cervical softening with dinoprostone gel on outcome of oxytocin-induced labor. Clinical Therapeutics 1993;15:838-44.

Yonekura ML, Songster G, Smith-Wallace T. Preinduction cervical priming with PGE2 intracervical gel. American Journal of Perinatology 1985;2:305-10.

Troostwijk 1992{Solo datos publicados}
Troostwijk AL, van Veen JB, Doesburg WH. Pre-induction intracervical application of a highly viscous prostaglandin E2 gel in pregnant women with an unripe uterine cervix: a double-blind placebo-controlled trial. European Journal of Obstetrics & Gynecology and Reproductive Biology 1992;43:105-11.

Ulmsten 1982{Solo datos publicados}
Ulmsten U, Wingerup L, Belfrage P, Ekman G, Wiqvist N. Intracervical application of prostaglandin gel for induction of term labor. Obstetrics & Gynecology 1982;59:336-9.

Ulmsten 1985{Solo datos publicados}
Ulmsten U, Ekman G, Belfrage P, Bygdeman M, Nyberg C. Intracervical versus intravaginal PGE2 for induction of labor at term in patients with an unfavorable cervix. Archives of Gynecology 1985;236:243-8.

Wieland 1999{Solo datos publicados}
Wieland D, Friedman F. Comparing two dinoprostone agents for preinduction cervical ripening at term. A randomized trial. Journal of Reproductive Medicine 1999;44:724-8.

Wingerup 1978{Solo datos publicados}
Wingerup L, Andersson KE, Ulmsten U. Ripening of the uterine cervix and induction of labour at term with prostaglandin E2 in viscous gel. Acta Obstetricia et Gynecologica Scandinavica 1978;57:403-6.

Yuen 1996{Solo datos publicados}
*Yuen PM, Pang HYY, Chung T, Chang A. Cervical ripening before induction of labour in patients with an unfavourable cervix. A comparative randomised study of the Atad Ripener device, Prostaglandin E2 vaginal pessary and prostglandin E2 intracervical gel. Australian and New Zealand Journal of Obstetrics and Gynaecology 1996;36:291-5.

Yuen PM, Pang YYH. A randomized study of two different methods for cervical ripening. Proceedings of 2nd International Scientific Meeting of the Royal College of Obstetricians and Gynaecologists; 1993 Sept 7-10; Hong Kong. 1993:154.

Zanini 1989{Solo datos publicados}
Zanini A, Ghidini A, Norchi S, Beretta E, Cortinovis I, Bottino S. Pre-induction cervical ripening with prostaglandin E2 gel: intracervical versus intravaginal route. Obstetrics & Gynecology 1990;76:681-3.

*Zanini A, Norchi S, Beretta E, Cortinovis I, Fenaroli G, Scian A. Cervical ripening and induction of labor in term pregnancy using prostaglandin E2. Controlled clinical study comparing the intracervical and intravaginal routes [Maturazione cervicale e induzione del travaglio di parto in gravidanze a termine con prostaglandina E2. Studio clinico controllato tra via intracervicale e intravaginale]. Annali di Ostetricia, Ginecologia, Medicina Perinatale 1989;110:209-16.


Aggarwal 2006
Aggarwal N, Kirthika KS, Suri V, Malhotra S. Comparative evaluation of vaginal PGE-1 analogue (misoprostol) and intracervical PGE-2 gel for cervical ripening and induction of labor [abstract]. 49th All India Congress of Obstetrics and Gynaecology; 2006 Jan 6-9; Cochin, Kerala State, India. 2006:95.

Bredow 1993
Bredow V, Straube W. Fetal outcome following to cervical condition appropriated induction of labour with prostaglandin E2 in correlation to cervical condition. Zentralblatt fur Gynakologie 1993;115:530-6.

Cararach 1994
*Cararach V, Sentis J, Botet F, Costa J, Manau D, Arimany MC. Cervical prostaglandin E2 compared with expectant management or systematic induction in PROM with bad cervical conditions. Proceedings of 14th European Congress of Perinatal Medicine; 1994 June 5-8; Helsinki, Finland. 1994:405.

Cararach V, Sentis J, Botet F, Foradada C, Manau D, Figueras F, et al. Cervical prostaglandin E1 compared with expectant management and with systematic induction in PROM near term, with bad cervical conditions. I-maternal results. 3rd World Congress of Perinatal Medicine; 1996 Oct 20-24; San Francisco, USA. 1996:44.

Foradada C, Cararach V, Sentis J, Botet F, Manau D, Figueras F, et al. Cervical prostaglandin E1 compared with expectant management and with systematic induction in PROM near term, with bad cervical conditions. II-fetal and neonatal results [abstract]. 3rd World Congress of Perinatal Medicine; 1996 Oct 20-24; San Francisco, USA. 1996:51-2.

Mateos D, Cararach V, Sentis J, Botet F, Figueras F, Arimany MC, et al. Cervical prostaglandin E2 compared with expectant management or systematic induction in premature rupture of membranes with bad cervical conditions. Prenatal and Neonatal Medicine 1996;1 Suppl 1:85.

D'Aniello 2003
D'Aniello G, Bocchi C, Florio P, Ignacchiti E, Guidoni CG, Centini G, et al. Cervical ripening and induction of labor by prostaglandin e2: a comparison between intracervical gel and vaginal pessary. Journal of Maternal-Fetal & Neonatal Medicine 2003;14(3):158-62.

Egarter 1988
Egarter C, Husslein P. Sensitivity test before induction of labour using prostaglandin E2 vaginal tablets. Zentralblatt fur Gynakologie 1988;110:345-53.

Ekblad 1994
*Ekblad U, Erkkola R, Pirhonen J. Comparison of intravaginal and two intracervical prostaglandin E2 gels in pre-induction of labour. Annales Chirurgiae et Gynaecologiae 1994;83:64-7.

Facchinetti 2005
Facchinetti F, Venturini P, Verocchi G, Volpe A. Comparison of two preparations of dinoprostone for pre-induction of labour in nulliparous woman with very unfavourable cervical condition: a randomised clinical trial. European Journal of Obstetrics & Gynecology and Reproductive Biology 2005;119:189-93.

Fuchs 1984
Fuchs AR, Goeschen K, Rasmussen AB, Rehnstrom JV. Cervical ripening and plasma prostaglandin levels. Comparison of endocervical and extra-amniotic. Prostaglandins 1984;28(2):217-27.

Garcia 1988
Garcia AA, Chavez AJ, Jimenez SG, Isquierdo PJC, Angles WD, Santos GJ, et al. Preinduction cervical ripening with PGE2: a double blind study. 12th FIGO World Congress of Gynecology and Obstetrics; 1988 October 23-28; Brazil. 1988:197.

Gittens 1996
Gittens L, Schenkel C, Strassberg S, Apuzzio J. Vaginal birth after cesarean section: comparison of outpatient use of prostaglandin gel to expectant management. American Journal of Obstetrics and Gynecology 1996;174(1 Pt 2):354.

Goeschen 1985
Goeschen K, Fuchs AR, Fuchs F, Rasmussen AB, Rehnstrom JV, Saling E. Effect of beta-mimetic tocolysis on cervical ripening and plasma prostaglandin F2alpha metabolite after endocervical application of prostaglandin E2. Obstetrics & Gynecology 1985;65:166-71.

Gonen 1994
*Gonen R, Samberg I, Degani S. Intracervical prostaglandin E2 for induction of labor in patients with premature rupture of membranes and an unripe cervix. American Journal of Perinatology 1994;11:436-8.

Gonen R, Samberg I, Degani S, Sharf M. Intracervical prostaglandin E2 for induction of labour in patients with premature rupture of membranes and an unfavourable cervix. American Journal of Obstetrics and Gynecology 1993;168:362.

Hennessey 1998
*Hennessey MH, Rayburn WF, Stewart JD, Liles EC. Pre-eclampsia and induction of labor: a randomized comparison of prostaglandin e2 as an intracervical gel, with oxytocin immediately, or as a sustained-release vaginal insert. American Journal of Obstetrics and Gynecology 1998;179(5):1204-9.

Stewart JD, Rayburn WF, Farmer K, Liles E, Schipul A, Stanley J. Effectiveness of prostaglandin E2 as an intracervical gel with immediate oxytocin, or as a sustained-release vaginal insert for induction of labour. American Journal of Obstetrics and Gynecology 1998;178(1 Pt 2):92.

Stewart JD, Rayburn WF, Farmer KC, Liles EM, Schipul AHJr, Stanley JR. Effectiveness of prostaglandin e2 intracervical gel (prepidil), with immediate oxytocin, versus vaginal insert (cervidil) for induction of labor. American Journal of Obstetrics and Gynecology 1998;179(5):1175-80.

Henson 1987
Henson BV. Cervical ripening with prostaglandin E2. Personal communication. 1987.

Herabutya 1992
Herabutya Y, Prasertsawat PO, Tongyai T, Isarangura N, Ayudthya N. Prolonged pregnancy: the management dilemma. International Journal of Gynecology & Obstetrics 1992;37:253-8.

Herabutya 1993
Herabutya Y, Prasertsawat PO. Ripening of the unfavorable cervix with prostaglandin E2: intracervical versus intravaginal route. Journal of the Medical Association of Thailand 1993;76 Suppl 1:63-8.

Iftikhar 1991
Iftikhar M, Price J, Beattie RB, Heasley RN. Evaluation of PGE2 intracervical gel for cervical ripening in primigravidae with unfavourable cervicies. Proceedings of 2nd European Congress on Prostaglandins in Reproduction; 1991 April 30-May 3; The Hague, Netherlands. 1991:139.

*Iftikhar M, Price J, Beattie RB, Heasley RN, Armstrong MJ. Pre-induction cervical ripening in primigravida with unfavourable cervix. A randomised controlled trial using PGE2 intracervical gel or vaginal pessary. Journal of Perinatal Medicine 1992;20:96.

Ingemarsson 1991
Ingemarson I, Heden L, Montan S, Sjoberg NO. Prostaglandin gel for ripening of the cervix in post term pregnancy. Personal communication. 1991.

Kamat 2002
Kamat DS, Kamat VD, Mulary AA, Kharat A, Thomas EV. Induction and augmentation of labour by intracervical and/or intravaginal PGE2 tablet (Primiprost). Journal of Obstetrics and Gynecology of India 2002;52(5):33-4.

Kaminski 1994
Kaminski K, Rechberger T, Oleszczuk J, Jakowicki J, Oleszczuk J. Biochemical and clinical evaluation of the efficiency of intracervical extraamniotic prostaglandin F2 and intravenous oxytocin infusion to induce labour at term. Australian and New Zealand Journal of Obstetrics and Gynaecology 1994;34:409-13.

Kupietz 1994
Kupietz R, Faber J, Heidegger H. Advantage of labor induction by intracervical prostaglandin E2 gel at night. Zentralblatt fur Gynakologie 1994;116:468-73.

Lotshaw 1994
Lotshaw RR, Gordon HR. Optimal interval between prostaglandin E2 ripening of the cervix and oxytocin induction of labor: a prospective clinical trial. Journal of Maternal-Fetal Medicine 1994;3:153-6.

Luther 1983
Luther ER. Comparison of natural and synthetic PGE2 tablets in labour induction. Canadian Medical Association Journal 1983;128:1189-91.

Lyndrup 1992
Lyndrup J, Legarth J, Weber T, Nickelsen C, Guldbaek E. Predictive value of pelvic scores for induction of labor by local PGE2. European Journal of Obstetrics & Gynecology and Reproductive Biology 1992;47:17-23.

Mackenzie 1988
Mackenzie IZ, Annan B, Jackson C, Hurley P, Hey F, Newman M. A randomized trial comparing a non-biodegradable polymer PGE2 pessary with a glyceride PGE2 pessary for labour induction. 12th FIGO World Congress of Gynecology and Obstetrics; 1988 October 23-28; Brazil. 1988:199.

Megalo 1998
Megalo A, Holhfeld P. Misoprostol (PGE1) as an alternative to PGE2 for pre-induction cervical ripening and labour induction. 21st Conference of the Swiss Society of Gynecology and Obstetrics; 1998. 1998:19.

Minaretzis 1993
Minaretzis D, Tsionu C, Papageorgiou I, Michalas S, Aravantinos D. Intracervical prostaglandin E2 gel for cervical ripening and labor induction: what is the appropriate dose?. Gynecologic and Obstetric Investigation 1993;35:34-7.

Mink 1994
Mink D, Boos R, Heiss C, Schmidt W. PgE2 gel and PgE2 vaginal tablets for induced labor--a prospective randomized study. Geburtshilfe und Frauenheilkunde 1994;54:409-13.

Muller 1995
Muller T, Rempen A. Induced labor with prostaglandins: 0.5 mg PGE2 intracervical gel versus 3 mg PGE2 vaginal tablet. Zeitschrift fur Geburtshilfe und Perinatologie 1995;199:30-4.

Muller 2000
Muller T, Schildhauer K, Gross M, Dietl J. Induction of labour with prostaglandins with unripe cervix: 0.5mg intracervical PG-E2 versus 3 mg PG-E2 vaginal tablet [Gebursteinleitung mit Prostaglandinen bei unreifer Zervix: 0.5 mg PGE2 Intrazervicalgel versus 3 mg PGE2 Vaginal-tablette]. Geburtshilfe und Frauenheilkunde 2000;60(Suppl 1):S71.

Noah 1985
Noah ML, Thiery M, Parewijck W, Decoster JM. Assessment of a two dose scheme of PGE2 gel for preinduction cervical softening. Prostaglandins 1985;30:305-11.

Nuutila 1997
Nuutila M, Cacciatore B, Ylikorkala O. Effect of local prostaglandin E2 on uterine and fetal Doppler flow in pregnancy-induced hypertension. Hypertension in Pregnancy 1997;16:357-66.

Parewijck 1987
Parewijck W. Cervical ripening with intracervical application of prostaglandin E2 gel. Personal communication. 1987.

Paul 1988
Paul R, Romero R. Clinical trial of induction vs expectant management in post-term pregnancy. Personal communication. 1988.

Penna 1991
Penna LK, MacLachlan NA, Dunlop D, Spencer JAD. Intracervical or intravaginal prostaglandin E2 gel for cervical ripening in the unfavourable cervix - a randomised trial. Proceedings of 2nd European Congress on Prostaglandins in Reproduction; 1991 April 30-May 3; The Hague, Netherlands. 1991:141.

Polvi 1994
Polvi HJ, Pirhonen JP, Erkkola RU. Vaginal and intracervical prostaglandin E2 for cervical ripening: a doppler study of hemodynamic effects. American Journal of Perinatology 1994;11:337-9.

Rath 1985
Rath W, Adelmann-Grill BC, Schauer A, Hilgers R, Harder D, Kuhn W. Clinical, morphological and biochemical aspects of cervical ripening by intracervically applied sulprostone-gel. Archives of Gynecology 1985;237(Suppl 1):342.

Rayburn 1988
Rayburn W, Gosen R, Ramadei C, Woods R, Scott J. Outpatient cervical ripening with prostaglandin E2 gel in uncomplicated postdate pregnancies. American Journal of Obstetrics and Gynecology 1988;158:1417-23.

Rayburn 1999
Rayburn W, Lucas M, Gittens L, Goodwin TM, Baxi L, Gall S, et al. Attempted vaginal birth after cesarean section: a multicenter comparison of outpatient prostaglandin E2 gel with expectant management [abstract]. Primary Care Update for Ob/Gyns 1998;5(4):182-3.

*Rayburn WF, Gittens LN, Lucas MJ, Gall SA, Martin ME. Weekly administration of prostaglandin e2 gel compared with expectant management in women with previous cesareans. Prepidil gel study group. Obstetrics & Gynecology 1999;94(2):250-4.

Reichel 1985
Reichel R, Husslein P, Goschen K, Rasche M, Sinzinger H. Resorption of prostaglandin e2 following various methods of local administration for ripening of the cervix and end the induction of labor. Wiener Klinische Wochenschrift 1985;97(11):500-3.

Roberts 1986
Morrison JC. Cervical ripening techiques. Personal communication. 1993.

*Roberts WE, North DH, Speed JE, Martin JN, Palmer SM, Morrison JC. Comparative study of prostaglandin, laminaria and minidose oxytocin for ripening of the unfavourable cervix prior to induction of labour. Journal of Perinatology 1986;6:16-9.

Sahraoui 2005
Sahraoui W, Hajji S, Bibi M, Nouira M, Essaidi H, Khair H. Management of pregnancies beyond forty-one week's gestation with an unfavorable cervix. Journal de Gynecologie, Obstetrique et Biologie de la Reproduction 2005;34(5):454-62.

Sanchez-Ramos 1995
*Sanchez-Ramos L, Farah LA, Kaunitz AM, Adair CD, Del Valle GO, Fuqua P. Preinduction cervical ripening with commercially available prostaglandin E2 gel: a randomized, double-blind comparison with a hospital-compounded preparation. American Journal of Obstetrics and Gynecology 1995;173:1079-84.

Sanchez-Ramos L, Farah LA, Kaunitz AM, Adair CD, Walker C, Del Valle GO, et al. Preinduction cervical ripening with commercially available prostaglandin E2 gel: a randomized, double-blind comparison with a hospital-compounded preparation. American Journal of Obstetrics and Gynecology 1995;172:298.

Schneider 1994
Schneider KTM, Luftner D, Rath W. Efficacy and safety of a 2-tier prostaglandin labor induction schedule. Journal of Perinatal Medicine 1994;22:399-407.

Shaala 1989
Shaala S, Darwish E, Anwar M, Rocca M, Ismail AA. Cervical prostaglandin injection: a novel method of administration for ripening the cervix and induction of labor. International Journal of Gynecology & Obstetrics 1989;30:221-3.

Skajaa 1991
Skajaa K, Mamsen A, Secher NJ. Cervical ripening with prostaglandin E2 in different vehicle forms. Proceedings of 1st European Congress on Prostaglandins in Reproduction; 1988 July 6-9; Vienna, Austria. 1988:196.

*Skajaa K, Mamsen A, Secher NJ. Influence of vehicle form on efficiency of prostaglandin E2 gel for cervical ripening. European Journal of Obstetrics & Gynecology and Reproductive Biology 1991;42:177-80.

Tey 1995
Tey A, Eriksen NL, Blanco JD. A prospective randomised trial of induction versus expectant management in nondiabetic pregnancies with macrosomia. American Journal of Obstetrics and Gynecology 1995;172:293.

van Dessel 1991
van Dessel T, Frijns JHM, Kok FTJGT, Wallenburg HCS. Prostaglandins and dilatation of the human cervix. Proceedings of 2nd European Congress on Prostaglandins in Reproduction; 1991 April 30-May 3; The Hague, Netherlands. 1991:121.

Voss 1996
Voss DH, Cumminsky KC, Cook VD, Nethers MS, Spinnato JA, Gall SA. Effect of three concentrations of intracervical prostaglandin E2 gel for cervical ripening. Journal of Maternal-Fetal Medicine 1996;5:186-93.

Webb 1997
Webb GW, Raynor BD, Huddleston JF, Fandall HW. Induction of labour with an unfavourable cervix: a randomized prospective trial. American Journal of Obstetrics and Gynecology 1997;176:22.

Williams 1985
Williams JK, Wilkerson WG, O'Brien WF, Knuppel RA. Use of prostaglandin E2 topical cervical gel in high-risk patients: a critical analysis. Obstetrics & Gynecology 1985;66:769-73.

Wyldes 1992
Wyldes MP. Trial to compare 0.5mg PGE2 intracervical gel (Prepadil) vs vaginal PGE2 gel (1mg or 2mg) in induction of labour. Personal communication. 2007.

Yacoob 1993
Yacoob T, Lloyd M, Unwin A, Harrison RF. Intracervical prostaglandin E2, 0.5mg; gel or tablet for cervical ripening and induction of labour with an unfavourable cervix?. Journal of Obstetrics and Gynaecology 1993;13:167-70.


Alfirevic 2006
Alfirevic Z, Weeks A. Oral misoprostol for induction of labour. In: Cochrane Database of Systematic Reviews, 2, 2006.  10.1002/14651858.CD001338.pub2.

Boulvain 2001a
Boulvain M, Kelly A, Lohse C, Stan C, Irion O. Mechanical methods for induction of labour. In: Cochrane Database of Systematic Reviews, 4, 2001.  10.1002/14651858.CD001233.

Boulvain 2001b
Boulvain M, Stan C, Irion O. Elective delivery in diabetic pregnant women. In: Cochrane Database of Systematic Reviews, 2, 2001.  10.1002/14651858.CD001997.

Boulvain 2005
Boulvain M, Stan C, Irion O. Membrane sweeping for induction of labour. In: Cochrane Database of Systematic Reviews, 1, 2005.  10.1002/14651858.CD000451.pub2.

Bricker 2000
Bricker L, Luckas M. Amniotomy alone for induction of labour. In: Cochrane Database of Systematic Reviews, 4, 2000.  10.1002/14651858.CD002862.

Chez 1995
Chez RA. Cervical ripening and labor induction after previous cesarean delivery. Clinical Obstetrics and Gynecology 1995;38:287-92.

Curtis 1987
Curtis P, Evans S, Resnick J. Uterine hyperstimulation. The need for standard terminology. Journal of Reproductive Medicine 1987;32:91-5.

Flenady 2002
Flenady V, King J. Antibiotics for prelabour rupture of membranes at or near term. In: Cochrane Database of Systematic Reviews, 3, 2002.  10.1002/14651858.CD001807.

French 2001
French L. Oral prostaglandin E2 for induction of labour. In: Cochrane Database of Systematic Reviews, 2, 2001.  10.1002/14651858.CD003098.

Gülmezoglu 2006
Gülmezoglu AM, Crowther CA, Middleton P. Induction of labour for improving birth outcomes for women at or beyond term. In: Cochrane Database of Systematic Reviews, 4, 2006.  10.1002/14651858.CD004945.pub2.

Higgins 2006
Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions 4.2.6 [updated September 2006]. In: The Cochrane Library, Issue 4, 2006. Chichester, UK: John Wiley & Sons, Ltd. .

Hofmeyer 2003
Hofmeyer GJ, Gulmezoglu AM. Vaginal misoprostol for cervical ripening and induction of labour. In: Cochrane Database of Systematic Reviews, 1, 2003.  10.1002/14651858.CD000941.

Hofmeyr 2000
Hofmeyr GJ, Alfirevic Z, Kelly T, Kavanagh J, Thomas J, Brocklehurst P, et al. Methods for cervical ripening and labour induction in late pregnancy: generic protocol. In: Cochrane Database of Systematic Reviews, 2, 2000.  10.1002/14651858.CD002074.

Hofmeyr 2003
Hofmeyr GJ, Gülmezoglu AM. Vaginal misoprostol for cervical ripening and induction of labour. In: Cochrane Database of Systematic Reviews, 1, 2003.  10.1002/14651858.CD000941.

Howarth 2001
Howarth GR, Botha DJ. Amniotomy plus intravenous oxytocin for induction of labour. In: Cochrane Database of Systematic Reviews, 3, 2001.  10.1002/14651858.CD003250.

Huszar 1984
Huszar G, Naftolin F. The myometrium and uterine cervix in normal and preterme labour. New England Journal of Medicine 1984;311(9):571-81.

Hutton 2001
Hutton E, Mozurkewich E. Extra-amniotic prostaglandin for induction of labour. In: Cochrane Database of Systematic Reviews, 2, 2001.  10.1002/14651858.CD003092.

Irion 1998a
Irion O, Boulvain M. Induction of labour for suspected fetal macrosomia. In: Cochrane Database of Systematic Reviews, 2, 1998.  10.1002/14651858.CD000938.

Kavanagh 2001b
Kavanagh J, Kelly AJ, Thomas J. Sexual intercourse for cervical ripening and induction of labour. In: Cochrane Database of Systematic Reviews, 2, 2001.  10.1002/14651858.CD003093.

Kavanagh 2005
Kavanagh J, Kelly AJ, Thomas J. Breast stimulation for cervical ripening and induction of labour. In: Cochrane Database of Systematic Reviews, 3, 2005.  10.1002/14651858.CD003392.pub2.

Kavanagh 2006a
Kavanagh J, Kelly AJ, Thomas J. Corticosteroids for cervical ripening and induction of labour. In: Cochrane Database of Systematic Reviews, 2, 2006.  10.1002/14651858.CD003100.pub2.

Kavanagh 2006b
Kavanagh J, Kelly AJ, Thomas J. Hyaluronidase for cervical ripening and induction of labour. In: Cochrane Database of Systematic Reviews, 2, 2006.  10.1002/14651858.CD003097.pub2.

Keirse 1993
Keirse MJ. Prostaglandins in preinduction cervical ripening. Meta-analysis of worldwide clinical experience. Journal of Reproductive Medicine 1993;38:89-100.

Kelly 2001a
Kelly AJ, Tan B. Intravenous oxytocin alone for cervical ripening and induction of labour. In: Cochrane Database of Systematic Reviews, 3, 2001.  10.1002/14651858.CD003246.

Kelly 2001b
Kelly AJ, Kavanagh J, Thomas J. Castor oil, bath and/or enema for cervical priming and induction of labour. In: Cochrane Database of Systematic Reviews, 2, 2001.  10.1002/14651858.CD003099.

Kelly 2001c
Kelly AJ, Kavanagh J, Thomas J. Relaxin for cervical ripening and induction of labour. In: Cochrane Database of Systematic Reviews, 2, 2001.  10.1002/14651858.CD003103.

Kelly 2003
Kelly AJ, Kavanagh J, Thomas J. Vaginal prostaglandin (PGE2 and PGF2a) for induction of labour at term. In: Cochrane Database of Systematic Reviews, 4, 2003.  10.1002/14651858.CD003101.

Kelly 2008
Kelly 2008. Nitric oxide donors for cervical ripening and induction of labour. In: Cochrane Database of Systematic Reviews, 1, 2008.  10.1002/14651858.CD006901.

Luckas 2000
Luckas M, Bricker L. Intravenous prostaglandin for induction of labour. In: Cochrane Database of Systematic Reviews, 4, 2000.  10.1002/14651858.CD002864.

Mastrogiannis 1995
Mastrogiannis DS, Knuppel RA. Labor induced using methods that do not involve oxytocin. Clinical Obstetrics and Gynecology 1995;38:259-66.

Muzonzini 2004
Muzonzini G, Hofmeyr GJ. Buccal or sublingual misoprostol for cervical ripening and induction of labour. In: Cochrane Database of Systematic Reviews, 4, 2004.  10.1002/14651858.CD004221.pub2.

Neilson 2000
Neilson JP. Mifepristone for induction of labour. In: Cochrane Database of Systematic Reviews, 4, 2000.  10.1002/14651858.CD002865.

Raskin 1999
Raskin KS, Dachauer JD, Doeden AL, Rayburn WF. Uterine rupture after use of a prostaglandin E2 vaginal insert during vaginal birth after cesarean. A report of two cases. Journal of Reproductive Medicine 1999;44(6):571-4.

Rath 1993
Rath W, Osmers R, Adelmann-Grill BC, Stuhlsatz HW, Szevereny M, Kuhn W. Biochemical changes in human cervical tissue after intracervical application of prostaglandins E2. Prostaglandins 1993;45:375-84.

RCOG 2007
Varma M, Gupta JK, Smith GCS. Birth after previous caesarean birth. RCOG Green-top Guideline No. 45. 2007.

RevMan 2003
The Nordic Cochrane Centre. Review Manager (RevMan). 4.2 for Windows. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration. 2003.

Smith 2003
Smith CA. Homoeopathy for induction of labour. In: Cochrane Database of Systematic Reviews, 4, 2003.  10.1002/14651858.CD003399.

Thomas 2001
Thomas J, Kelly AJ, Kavanagh J. Oestrogens alone or with amniotomy for cervical ripening or induction of labour. In: Cochrane Database of Systematic Reviews, 4, 2001.  10.1002/14651858.CD003393.

Vause 1999
Vause S, Macintosh M. Use of prostaglandins to induce labour in women with a caesarean section scar. BMJ 1999;318:1056-8.

* El asterisco señala los documentos más importantes para este estudio



GRÁFICOS
Para visualizar un gráfico o una tabla, haga clic en la medida de resultado que aparece en la tabla de abajo.

Para visualizar los gráficos mediante el Metaview, haga clic en "Visualizar Metaview" en el encabezado del gráfico.


01 Intracervical prostaglandin (PGE2) vs placebo/no treatment: all women
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
01 Vaginal delivery not achieved within 24 hours4198Relative Risk (Fixed) 95% CI0.61 [0.47, 0.79]
02 Uterine hyperstimulation with fetal heart rate changes122296Relative Risk (Fixed) 95% CI1.21 [0.72, 2.05]
03 Caesarean section273734Relative Risk (Fixed) 95% CI0.88 [0.77, 1.00]
04 Serious neonatal morbidity or perinatal death41193Relative Risk (Fixed) 95% CI0.75 [0.19, 2.96]
05 Serious maternal morbidity or death21081Relative Risk (Fixed) 95% CI0.33 [0.01, 7.96]
06 Cervix unfavourable/unchanged after 12-24 hours145Relative Risk (Fixed) 95% CINot estimable
07 Oxytocin augmentation184Relative Risk (Fixed) 95% CI0.67 [0.40, 1.12]
08 Uterine hyperstimulation without fetal heart rate changes112531Relative Risk (Fixed) 95% CI1.59 [1.09, 2.33]
11 Instrumental vaginal delivery7551Relative Risk (Fixed) 95% CI1.03 [0.70, 1.50]
12 Meconium stained liquor3416Relative Risk (Fixed) 95% CI1.20 [0.80, 1.81]
13 Apgar score < 7 at 5 minutes142553Relative Risk (Fixed) 95% CI0.91 [0.62, 1.34]
14 Neonatal intensive care unit admission4261Relative Risk (Fixed) 95% CI0.32 [0.10, 1.07]
16 Perinatal death21081Relative Risk (Fixed) 95% CI0.20 [0.01, 4.05]
18 Maternal side-effects (all)101425Relative Risk (Fixed) 95% CI1.18 [0.95, 1.47]
19 Nausea3199Relative Risk (Fixed) 95% CI2.00 [0.19, 21.47]
20 Vomiting41015Relative Risk (Fixed) 95% CI2.27 [1.11, 4.63]
21 Diarrhoea3307Relative Risk (Fixed) 95% CI1.13 [0.23, 5.65]
23 Postpartum haemorrhage4623Relative Risk (Fixed) 95% CI3.27 [0.82, 13.03]
24 Serious maternal complications184Relative Risk (Fixed) 95% CI1.05 [0.22, 4.90]
25 Maternal death1816Relative Risk (Fixed) 95% CINot estimable
02 Intracervical prostaglandin (PGE2) vs placebo/no treatment: all women, unfavourable cervix
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
01 Vaginal delivery not achieved within 24 hours4198Relative Risk (Fixed) 95% CI0.61 [0.47, 0.79]
02 Uterine hyperstimulation with fetal heart rate changes122296Relative Risk (Fixed) 95% CI1.21 [0.72, 2.05]
03 Caesarean section273716Relative Risk (Fixed) 95% CI0.88 [0.77, 1.01]
04 Serious neonatal morbidity or perinatal death41193Relative Risk (Fixed) 95% CI0.75 [0.19, 2.96]
05 Serious maternal morbidity or death21081Relative Risk (Fixed) 95% CI0.33 [0.01, 7.96]
06 Cervix unfavourable/unchanged after 12-24 hours145Relative Risk (Fixed) 95% CINot estimable
07 Oxytocin augmentation184Relative Risk (Fixed) 95% CI0.67 [0.40, 1.12]
08 Uterine hyperstimulation without fetal heart rate changes112531Relative Risk (Fixed) 95% CI1.59 [1.09, 2.33]
11 Instrumental vaginal delivery7551Relative Risk (Fixed) 95% CI1.03 [0.70, 1.50]
12 Meconium stained liquor3416Relative Risk (Fixed) 95% CI1.20 [0.80, 1.81]
13 Apgar score < 7 at 5 minutes142553Relative Risk (Fixed) 95% CI0.91 [0.62, 1.34]
14 Neonatal intensive care unit admission4261Relative Risk (Fixed) 95% CI0.32 [0.10, 1.07]
16 Perinatal death21081Relative Risk (Fixed) 95% CI0.20 [0.01, 4.05]
18 Maternal side-effects (all)101425Relative Risk (Fixed) 95% CI1.18 [0.95, 1.47]
19 Nausea3199Relative Risk (Fixed) 95% CI2.00 [0.19, 21.47]
20 Vomiting41015Relative Risk (Fixed) 95% CI2.27 [1.11, 4.63]
21 Diarrhoea3307Relative Risk (Fixed) 95% CI1.13 [0.23, 5.65]
23 Postpartum haemorrhage4623Relative Risk (Fixed) 95% CI3.27 [0.82, 13.03]
24 Serious maternal complications184Relative Risk (Fixed) 95% CI1.05 [0.22, 4.90]
25 Maternal death1816Relative Risk (Fixed) 95% CINot estimable
03 Intracervical prostaglandin (PGE2) vs placebo/no treatment: all women, intact membranes, unfavourable cervix
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
01 Vaginal delivery not achieved within 24 hours2109Relative Risk (Fixed) 95% CI0.69 [0.45, 1.06]
02 Uterine hyperstimulation with fetal heart rate changes51413Relative Risk (Fixed) 95% CI0.84 [0.28, 2.57]
03 Caesarean section101869Relative Risk (Fixed) 95% CI0.82 [0.68, 0.98]
04 Serious neonatal morbidity or perinatal death1816Relative Risk (Fixed) 95% CI0.20 [0.01, 4.05]
05 Serious maternal morbidity or death1816Relative Risk (Fixed) 95% CI0.33 [0.01, 7.96]
06 Cervix unfavourable/unchanged after 12-24 hours00Relative Risk (Fixed) 95% CINot estimable
07 Oxytocin augmentation184Relative Risk (Fixed) 95% CI0.67 [0.40, 1.12]
08 Uterine hyperstimulation without fetal heart rate changes51406Relative Risk (Fixed) 95% CI1.97 [1.15, 3.38]
11 Instrumental vaginal delivery4363Relative Risk (Fixed) 95% CI1.11 [0.69, 1.80]
12 Meconium stained liquor184Relative Risk (Fixed) 95% CI0.70 [0.21, 2.30]
13 Apgar score < 7 at 5 minutes51153Relative Risk (Fixed) 95% CI0.70 [0.31, 1.55]
14 Neonatal intensive care unit admission184Relative Risk (Fixed) 95% CI1.05 [0.07, 16.22]
16 Perinatal death1816Relative Risk (Fixed) 95% CI0.20 [0.01, 4.05]
18 Maternal side-effects (all)3239Relative Risk (Fixed) 95% CI1.11 [0.45, 2.72]
19 Nausea2154Relative Risk (Fixed) 95% CI2.00 [0.19, 21.47]
20 Vomiting3970Relative Risk (Fixed) 95% CI2.25 [1.08, 4.67]
23 Postpartum haemorrhage180Relative Risk (Fixed) 95% CI3.00 [0.13, 71.51]
24 Serious maternal complications184Relative Risk (Fixed) 95% CI1.05 [0.22, 4.90]
25 Maternal death1816Relative Risk (Fixed) 95% CINot estimable
04 Intracervical prostaglandin (PGE2) vs placebo/no treatment: all women, ruptured membranes, unfavourable cervix
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
02 Uterine hyperstimulation with fetal heart rate changes171Relative Risk (Fixed) 95% CI1.03 [0.22, 4.76]
03 Caesarean section2159Relative Risk (Fixed) 95% CI1.02 [0.49, 2.15]
14 Neonatal intensive care unit admission171Relative Risk (Fixed) 95% CI0.11 [0.01, 2.05]
05 Intracervical prostaglandin (PGE2) v placebo/no treatment: all primiparae
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
01 Vaginal delivery not achieved within 24 hours289Relative Risk (Fixed) 95% CI0.55 [0.40, 0.75]
03 Caesarean section3122Relative Risk (Fixed) 95% CI1.27 [0.64, 2.52]
08 Uterine hyperstimulation without fetal heart rate changes139Relative Risk (Fixed) 95% CI1.05 [0.07, 15.66]
11 Instrumental vaginal delivery139Relative Risk (Fixed) 95% CI0.53 [0.15, 1.81]
13 Apgar score < 7 at 5 minutes289Relative Risk (Fixed) 95% CINot estimable
18 Maternal side-effects (all)150Relative Risk (Fixed) 95% CINot estimable
06 Intracervical prostaglandin (PGE2) vs placebo/no treatment: all primiparae, unfavourable cervix
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
01 Vaginal delivery not achieved within 24 hours139Relative Risk (Fixed) 95% CI0.47 [0.27, 0.81]
03 Caesarean section272Relative Risk (Fixed) 95% CI1.27 [0.64, 2.52]
08 Uterine hyperstimulation without fetal heart rate changes139Relative Risk (Fixed) 95% CI1.05 [0.07, 15.66]
11 Instrumental vaginal delivery139Relative Risk (Fixed) 95% CI0.53 [0.15, 1.81]
13 Apgar score < 7 at 5 minutes139Relative Risk (Fixed) 95% CINot estimable
07 Intracervical prostaglandin vs placebo/no treatment: all primiparae, intact membranes, unfavourable cervix
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
03 Caesarean section133Relative Risk (Fixed) 95% CI2.21 [0.90, 5.42]
11 Instrumental vaginal delivery00Relative Risk (Fixed) 95% CINot estimable
08 Intracervical prostaglandin (PGE2) vs placebo/no treatment: all multiparae
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
03 Caesarean section146Relative Risk (Fixed) 95% CI2.18 [0.44, 10.76]
11 Instrumental vaginal delivery00Relative Risk (Fixed) 95% CINot estimable
09 Intracervical prostaglandin (PGE2) vs placebo/no treatment: all multiparae, unfavourable cervix
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
03 Caesarean section146Relative Risk (Fixed) 95% CI2.18 [0.44, 10.76]
11 Instrumental vaginal delivery00Relative Risk (Fixed) 95% CINot estimable
10 Intracervical prostaglandin (PGE2) vs placebo/no treatment: all multiparae, intact memb, unfavourable cervix
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
03 Caesarean section146Relative Risk (Fixed) 95% CI2.18 [0.44, 10.76]
11 Instrumental vaginal delivery00Relative Risk (Fixed) 95% CINot estimable
11 Intracervical prostaglandin lower vs higher dose: all women
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
01 Caesarean section2112Relative Risk (Fixed) 95% CI0.79 [0.43, 1.44]
02 Uterine hyperstimulation with fetal heart rate changes184Relative Risk (Fixed) 95% CI1.20 [0.40, 3.63]
03 Oxytocin augmentation184Relative Risk (Fixed) 95% CI0.40 [0.24, 0.67]
12 Intracervical prostaglandin lower vs higher dose: all women, unfavourable cervix
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
01 Caesarean section2112Relative Risk (Fixed) 95% CI0.79 [0.43, 1.44]
02 Uterine hyperstimulation with fetal heart rate changes184Relative Risk (Fixed) 95% CI1.20 [0.40, 3.63]
03 Oxytocin augmentation184Relative Risk (Fixed) 95% CI0.40 [0.24, 0.67]
13 Intracervical prostaglandin lower vs higher dose: all primiparae, unfavourable cervix
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
01 Caesarean section128Relative Risk (Fixed) 95% CI1.30 [0.47, 3.62]
14 Intracervical prostaglandin lower vs higher dose: all primiparae
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
01 Caesarean section128Relative Risk (Fixed) 95% CI1.30 [0.47, 3.62]
20 Intracervical prostaglandin (PGE2) vs intravaginal prostaglandin (PGE2): all women
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
01 Vaginal delivery not achieved within 24 hours112200Relative Risk (Fixed) 95% CI1.26 [1.12, 1.41]
02 Uterine hyperstimulation with fetal heart rate changes131428Relative Risk (Fixed) 95% CI0.76 [0.39, 1.49]
03 Caesarean section283781Relative Risk (Fixed) 95% CI1.07 [0.93, 1.22]
04 Serious neonatal morbidity or perinatal death2168Relative Risk (Fixed) 95% CINot estimable
05 Serious maternal morbidity or death3415Relative Risk (Fixed) 95% CI3.07 [0.13, 74.71]
07 Oxytocin augmentation121958Relative Risk (Fixed) 95% CI1.02 [0.91, 1.16]
08 Uterine hyperstimulation without fetal heart rate changes131681Relative Risk (Fixed) 95% CI0.80 [0.56, 1.15]
09 Uterine rupture1247Relative Risk (Fixed) 95% CI3.07 [0.13, 74.71]
10 Epidural analgesia2315Relative Risk (Fixed) 95% CI1.07 [0.91, 1.25]
11 Instrumental vaginal delivery101130Relative Risk (Fixed) 95% CI0.90 [0.70, 1.16]
12 Meconium stained liquor3581Relative Risk (Fixed) 95% CI1.05 [0.52, 2.13]
13 Apgar score < 7 at 5 minutes152032Relative Risk (Fixed) 95% CI0.92 [0.51, 1.68]
14 Neonatal intensive care unit admission3423Relative Risk (Fixed) 95% CI0.94 [0.60, 1.46]
16 Perinatal death168Relative Risk (Fixed) 95% CINot estimable
18 Maternal side-effects (all)112810Relative Risk (Fixed) 95% CI1.13 [0.88, 1.44]
19 Nausea2473Relative Risk (Fixed) 95% CI0.90 [0.54, 1.50]
20 Vomiting3407Relative Risk (Fixed) 95% CI1.17 [0.66, 2.06]
21 Diarrhoea4646Relative Risk (Fixed) 95% CI4.94 [0.86, 28.54]
22 Other1247Relative Risk (Fixed) 95% CI0.51 [0.18, 1.46]
23 Postpartum haemorrhage4509Relative Risk (Fixed) 95% CI0.89 [0.55, 1.45]
24 Serious maternal complication1100Relative Risk (Fixed) 95% CINot estimable
26 Woman not satisfied1125Relative Risk (Fixed) 95% CI0.64 [0.11, 3.67]
21 Intracervical prostaglandin (PGE2) vs intravaginal prostaglandin (PGE2): all women, unfavourable cervix
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
01 Vaginal delivery not achieved within 24 hours101918Relative Risk (Fixed) 95% CI1.26 [1.12, 1.42]
02 Uterine hyperstimulation with fetal heart rate changes121146Relative Risk (Fixed) 95% CI0.85 [0.42, 1.73]
03 Caesarean section263586Relative Risk (Fixed) 95% CI1.06 [0.93, 1.21]
04 Serious neonatal morbidity or perinatal death1100Relative Risk (Fixed) 95% CINot estimable
05 Serious maternal morbidity or death2347Relative Risk (Fixed) 95% CI3.07 [0.13, 74.71]
07 Oxytocin augmentation91501Relative Risk (Fixed) 95% CI0.96 [0.85, 1.10]
08 Uterine hyperstimulation without fetal heart rate changes101257Relative Risk (Fixed) 95% CI0.82 [0.56, 1.21]
09 Uterine rupture1247Relative Risk (Fixed) 95% CI3.07 [0.13, 74.71]
10 Epidural analgesia1247Relative Risk (Fixed) 95% CI1.06 [0.91, 1.24]
11 Instrumental vaginal delivery9937Relative Risk (Fixed) 95% CI0.91 [0.69, 1.20]
12 Meconium stained liquor2299Relative Risk (Fixed) 95% CI0.90 [0.41, 1.97]
13 Apgar score < 7 at 5 minutes131682Relative Risk (Fixed) 95% CI0.93 [0.49, 1.74]
18 Maternal side-effects (all)102742Relative Risk (Fixed) 95% CI1.17 [0.91, 1.50]
19 Nausea2473Relative Risk (Fixed) 95% CI0.90 [0.54, 1.50]
20 Vomiting3407Relative Risk (Fixed) 95% CI1.17 [0.66, 2.06]
21 Diarrhoea4646Relative Risk (Fixed) 95% CI4.94 [0.86, 28.54]
22 Other1247Relative Risk (Fixed) 95% CI0.51 [0.18, 1.46]
23 Postpartum haemorrhage2154Relative Risk (Fixed) 95% CI1.71 [0.23, 12.66]
24 Serious maternal complication1100Relative Risk (Fixed) 95% CINot estimable
26 Woman not satisfied1125Relative Risk (Fixed) 95% CI0.64 [0.11, 3.67]
22 Intracervical prostaglandin (PGE2) vs intravaginal prostaglandin (PGE2): all women favourable cervix
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
03 Caesarean section1125Relative Risk (Fixed) 95% CI2.10 [0.20, 22.55]
11 Instrumental vaginal delivery1282Relative Risk (Fixed) 95% CI0.93 [0.49, 1.76]
24 Intracervical prostaglandin (PGE2) vs intravaginal prostaglandin (PGE2): all women, intact, unfavour cervix
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
01 Vaginal delivery not achieved within 24 hours5801Relative Risk (Fixed) 95% CI1.13 [0.96, 1.33]
02 Uterine hyperstimulation with fetal heart rate changes8906Relative Risk (Fixed) 95% CI0.93 [0.44, 1.96]
03 Caesarean section131609Relative Risk (Fixed) 95% CI1.00 [0.80, 1.25]
04 Serious neonatal morbidity or perinatal death1100Relative Risk (Fixed) 95% CINot estimable
05 Serious maternal morbidity or death2347Relative Risk (Fixed) 95% CI3.07 [0.13, 74.71]
07 Oxytocin augmentation71098Relative Risk (Fixed) 95% CI0.93 [0.78, 1.11]
08 Uterine hyperstimulation without fetal heart rate changes5592Relative Risk (Fixed) 95% CI0.65 [0.24, 1.72]
09 Uterine rupture1247Relative Risk (Fixed) 95% CI3.07 [0.13, 74.71]
10 Epidural analgesia1247Relative Risk (Fixed) 95% CI1.06 [0.91, 1.24]
11 Instrumental vaginal delivery5776Relative Risk (Fixed) 95% CI0.89 [0.65, 1.23]
12 Meconium stained liquor2355Relative Risk (Fixed) 95% CI1.45 [0.47, 4.46]
13 Apgar score < 7 at 5 minutes81061Relative Risk (Fixed) 95% CI0.82 [0.37, 1.86]
14 Neonatal intensive care unit admission2355Relative Risk (Fixed) 95% CI0.99 [0.62, 1.60]
18 Maternal side-effects (all)61539Relative Risk (Fixed) 95% CI1.06 [0.79, 1.41]
19 Nausea1247Relative Risk (Fixed) 95% CI0.89 [0.52, 1.54]
20 Vomiting3407Relative Risk (Fixed) 95% CI1.17 [0.66, 2.06]
21 Diarrhoea2347Relative Risk (Fixed) 95% CI3.07 [0.13, 74.71]
22 Other1247Relative Risk (Fixed) 95% CI0.51 [0.18, 1.46]
23 Postpartum haemorrhage3436Relative Risk (Fixed) 95% CI0.88 [0.54, 1.45]
24 Serious maternal complication1100Relative Risk (Fixed) 95% CINot estimable
25 Intracervical prostaglandin (PGE2) vs intravaginal prostaglandin (PGE2): all women, intact, favourable cervix
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
01 Uterine hyperstimulation with fetal heart rate changes00Relative Risk (Fixed) 95% CINot estimable
02 Maternal side-effects (all)00Relative Risk (Fixed) 95% CINot estimable
03 Caesarean section1125Relative Risk (Fixed) 95% CI2.10 [0.20, 22.55]
11 Instrumental vaginal delivery1282Relative Risk (Fixed) 95% CI0.93 [0.49, 1.76]
26 Intracervical prostaglandin (PGE2) vs intravaginal prostaglandin (PGE2): all women, intact, variable cervix
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
01 Vaginal delivery not achieved within 24 hours1282Relative Risk (Fixed) 95% CI1.07 [0.72, 1.57]
02 Uterine hyperstimulation with fetal heart rate changes1282Relative Risk (Fixed) 95% CI0.33 [0.03, 3.12]
03 Caesarean section2350Relative Risk (Fixed) 95% CI1.26 [0.62, 2.59]
04 Serious neonatal morbidity or perinatal death168Relative Risk (Fixed) 95% CINot estimable
05 Serious maternal morbidity or death168Relative Risk (Fixed) 95% CINot estimable
07 Oxytocin augmentation2350Relative Risk (Fixed) 95% CI1.06 [0.67, 1.66]
08 Uterine hyperstimulation without fetal heart rate changes2350Relative Risk (Fixed) 95% CI0.76 [0.24, 2.46]
10 Epidural analgesia168Relative Risk (Fixed) 95% CI1.14 [0.62, 2.11]
11 Instrumental vaginal delivery2350Relative Risk (Fixed) 95% CI1.06 [0.66, 1.71]
12 Meconium stained liquor1282Relative Risk (Fixed) 95% CI1.97 [0.37, 10.59]
13 Apgar score < 7 at 5 minutes2350Relative Risk (Fixed) 95% CI0.91 [0.14, 6.15]
14 Neonatal intensive care unit admission2350Relative Risk (Fixed) 95% CI0.87 [0.55, 1.38]
16 Perinatal death168Relative Risk (Fixed) 95% CINot estimable
18 Maternal side-effects (all)168Relative Risk (Fixed) 95% CI0.21 [0.02, 1.78]
23 Postpartum haemorrhage1282Relative Risk (Fixed) 95% CI0.87 [0.52, 1.45]
27 Intracervical prostaglandin (PGE2) vs intravaginal prostaglandin (PGE2): all primiparae
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
01 Vaginal delivery not achieved within 24 hours139Relative Risk (Fixed) 95% CI0.47 [0.27, 0.81]
02 Uterine hyperstimulation with fetal heart rate changes00Relative Risk (Fixed) 95% CINot estimable
03 Caesarean section3166Relative Risk (Fixed) 95% CI1.10 [0.58, 2.08]
04 Oxytocin augmentation00Relative Risk (Fixed) 95% CINot estimable
05 Serious maternal complication00Relative Risk (Fixed) 95% CINot estimable
08 Uterine hyperstimulation without fetal heart rate changes139Relative Risk (Fixed) 95% CI3.15 [0.14, 72.88]
11 Instrumental vaginal delivery3166Relative Risk (Fixed) 95% CI0.79 [0.45, 1.40]
13 Apgar score < 7 at 5 minutes139Relative Risk (Fixed) 95% CINot estimable
28 Intracervical prostaglandin (PGE2) vs intravaginal prostaglandin (PGE2): all primiparae, unfavourable cervix
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
01 Vaginal delivery not achieved within 24 hours139Relative Risk (Fixed) 95% CI0.47 [0.27, 0.81]
02 Uterine hyperstimulation with fetal heart rate changes00Relative Risk (Fixed) 95% CINot estimable
03 Caesarean section3166Relative Risk (Fixed) 95% CI1.10 [0.58, 2.08]
04 Oxytocin augmentation00Relative Risk (Fixed) 95% CINot estimable
05 Serious maternal complication00Relative Risk (Fixed) 95% CINot estimable
08 Uterine hyperstimulation without fetal heart rate changes139Relative Risk (Fixed) 95% CI3.15 [0.14, 72.88]
11 Instrumental vaginal delivery3166Relative Risk (Fixed) 95% CI0.79 [0.45, 1.40]
13 Apgar score < 7 at 5 minutes139Relative Risk (Fixed) 95% CINot estimable
29 Intracervical prostaglandin (PGE2) vs intravaginal prostaglandin (PGE2): all primiparae, intact, unfavourable
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
01 Vaginal delivery not achieved within 24 hours00Relative Risk (Fixed) 95% CINot estimable
02 Uterine hyperstimulation with fetal heart rate changes00Relative Risk (Fixed) 95% CINot estimable
03 Caesarean section2127Relative Risk (Fixed) 95% CI1.48 [0.68, 3.20]
04 Oxytocin augmentation00Relative Risk (Fixed) 95% CINot estimable
05 Serious maternal complication00Relative Risk (Fixed) 95% CINot estimable
11 Instrumental vaginal delivery2127Relative Risk (Fixed) 95% CI0.90 [0.47, 1.71]
30 Intracervical prostaglandin (PGE2) vs intravaginal prostaglandin (PGE2): all mulitiparae
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
03 Caesarean section2108Relative Risk (Fixed) 95% CI0.70 [0.18, 2.71]
11 Instrumental vaginal delivery2108Relative Risk (Fixed) 95% CI2.09 [0.32, 13.45]
31 Intracervical prostaglandin (PGE2) vs intravaginal prostaglandin (PGE2): all mulitiparae, unfavourable cervix
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
03 Caesarean section2108Relative Risk (Fixed) 95% CI0.70 [0.18, 2.71]
11 Instrumental vaginal delivery2108Relative Risk (Fixed) 95% CI2.09 [0.32, 13.45]
32 Intracervical prostaglandin (PGE2) vs intravaginal prostaglandin (PGE2): all mulitiparae, intact, unfavourable
Medida de resultadoNo. of studiesNo. of participantsStatistical methodEffect size
03 Caesarean section2108Relative Risk (Fixed) 95% CI0.70 [0.18, 2.71]
11 Instrumental vaginal delivery2108Relative Risk (Fixed) 95% CI2.09 [0.32, 13.45]


CARÁTULA
Titulo

Prostaglandinas intracervicales para la inducción del trabajo de parto

Autor(es)

Boulvain M, Kelly A, Irion O

Contribución de los autores

Tony Kelly realizó la recopilación inicial de datos, que fue actualizada por Rebecca Smyth. Michel Boulvain, Tony Kelly y Olivier Irion verificaron los datos y redactaron la revisión.

Número de protocolo publicado inicialmente2000/2
Número de revisión publicada inicialmente2008/1
Fecha de la modificación más recienteLa información no está disponible
Fecha de la modificación SIGNIFICATIVA más reciente14 noviembre 2007
Cambios más recientesEl autor no facilitó la información
Fecha de búsqueda de nuevos estudios no localizadosEl autor no facilitó la información
Fecha de localización de nuevos estudios aún no incluidos/excluidosEl autor no facilitó la información
Fecha de localización de nuevos estudios incluidos/excluidos31 agosto 2007
Fecha de modificación de la sección conclusiones de los autoresEl autor no facilitó la información
Dirección de contacto
Dr Michel Boulvain
Médecin adjoint agrégé
Unite de Developpement en Obstetrique
Hôpitaux Universitaires de Genève
CH-1211
Genève 14
SWITZERLAND
tel: + 41 22 3824317
michel.boulvain@hcuge.ch
fax: +41 22 3824424
Número de la Cochrane LibraryCD006971
Grupo editorialCochrane Pregnancy and Childbirth Group
Código del grupo editorialHM-PREG


FUENTES DE FINANCIACIÓN
Recursos externos
  • Department of Health Cochrane Review Incentive Scheme 2006 UK
Recursos internos
  • University of Geneva SWITZERLAND



Traducción realizada por el Centro Cochrane Iberoamericano.

Usado con permiso de John Wiley & Sons, Ltd.