Nitric Oxide Donor Isosorbide Mono Nitrate for Induction of Labor With Pre-labor Rupture of Membranes
Nitric Oxide Donor Isosorbide Mono Nitrate for Induction of Labor With Pre-labor Rupture of Membranes
The study aims to evaluate and assess the effectiveness and safety of vaginal administration
 of isosorbide mono nitrate (IMN) to induce cervical ripening and shorten the interval time
 between induction and delivery in women undergoing induction of labor at term or post term
 with prelabor rupture of membrane.

 Research Hypothesis:

 In women undergoing induction of labor at term or post term with pre-labor rupture of
 membrane, vaginal administration of isosorbide mono nitrate (IMN) is effective to induce
 cervical ripening and shorten the interval time between induction and delivery.

 Research Questions:

 Does vaginal administration of isosorbide mono nitrate (IMN) induce cervical ripening and
 shorten the interval time between induction and delivery in women undergoing induction of
 labor at term or post term with prelabor rupture of membrane?
-  Study Design: Prospective double blinded randomized placebo-controlled Clinical trial

 -  Time plan: Approximately 6 months according to calculated sample size.

 -  study setting: this study will be conducted obstetrics and gynecology department at
 Cairo university.

 -  study population: patient will be recruited in this study those attending labor ward for
 induction of labor in term or post term pregnancies in females with pre-labor rupture of
 membranes

 -  Methodology in details

 All women will be subjected to

 -History taking:

 -  Verbal consent.

 -  Detailed clinical history.

 -  Personal history: Name, Age, Parity, Occupation, Residency and Special habits.

 -  Present history: History of onset, course and duration of vaginal bleeding or bloody
 vaginal discharge, presence of uterine contraction, PROM, IUGR or any indication of
 induction of labor.

 -  Obstetric history: History of previous preterm labor, previous abortion, previous full
 term deliveries, RH incompatibility, mode of delivery and fetal outcome.

 -  Menstrual history: For estimation of gestational age using Naegele's rule, provided that
 she had regular cycles for the last three months before she got pregnant and was not
 taking contraceptive pills during this period and she was sure of her dates.

 Term pregnancy defined as delivery between 37 and 42 weeks of gestation. Gestational age was
 assessed from the menstrual history and confirmed by measurement of fetal crown-rump length
 at a first-trimester scan. Post-term pregnancy defined as delivery after 42 weeks of
 gestation.

 -  Past history: History of medical disorders, drug therapy or allergy or history of intake
 of other tocolytic drugs.

 -  Family history : For any similar condition

 -Examination

 -  Full clinical examination (pulse, temperature and the blood pressure).

 -  General examination including chest, heart and abdominal examination for fundal level.

 -  Local clinical examination; with special attention to pelvic examination to assess the
 state of the cervix (dilatation, effacement, PROM, station and presenting part) and to
 assess vaginal bleeding or amniotic fluid in vagina if present and to exclude
 cephalic-pelvic disproportion.

 -  Routine ante-natal investigations (Rh, Hb, fasting and postprandial blood sugar and
 complete urine analysis).(CBC with differential and CRP to exclude chorioamnionitis)

 -  Ultrasonography examination : to assess the following data:

 -  Gestational age

 -  Fetal viability

 -  Fetal presentation and EFW.

 -  Exclusion of any fetal congenital anomalies.

 -  To ensure that the all inclusion criteria are present.

 -  Check amniotic fluid index.

 -  Intervention:

 After admission for labor induction, cervical assessment is done to see dilatation (cm),
 length (cm), position, consistency, and station of presenting part to get the modified Bishop
 score and to confirm pre-labor rupture of membrane.

 In vaginal IMN group (group 1) 40 mg tablet of intra-vaginal IMN (Effox; MINAPHARMA, Cairo,
 Egypt) will be placed into the posterior fornix of the vagina, through a digital vaginal
 examination, every 4 h for a maximum of four doses. The medication will be stopped with the
 onset of labor. Oxytocin will be started 6 h after the last dose of IMN in women not in
 active phase of labor but have Bishop score is >6. Intravenous oxytocin is initiated at an
 infusion flow rate of 4 mIU/min and will be doubled as necessary, with 30-min intervals
 between increasing the doses, up to a maximum of 16 mIU/min. To obtain this concentration, 5
 IU of synthetic oxytocin are added to 500 ml of a 5% dextrose solution. Further management of
 labor will be done according to the hospitals protocols.

 In placebo group (group 2) 40 mg intra-vaginal pyridoxine placebos every 4 h for a maximum of
 four doses will be given, followed by intravenous oxytocin infusion and management of labor
 as in group 1.

 In both groups, the pregnant females who don't progress to labor (regular contractions with
 continued cervical changes) with no cervical changes ( bishop score equal to or less than 6)
 after a maximum of four doses and oxytocin infusion, this will be considered failure of
 induction and those patients will delivered by cesarean section.

 Subjects will be followed-up regularly after taking the medications by obstetricians who are
 unaware of the group to which the patient belongs. Uterine contraction and fetal heart rate
 (FHR) will be checked every 30 min. Prophylactic or "latency" antibiotics, typically
 ampicillin and erythromycin for prevention of chorioamnionitis. Symptoms and vital signs will
 be monitored at regular intervals. Subjects will be asked to report when they have uterine
 contraction or abnormal symptoms such as headache, nausea, shivering.

 signs of chorioamnionitis (e.g : fever, uterine fundal tenderness, maternal and fetal
 tachycardia, purulent or foul smelling discharge) will be checked at regular intervals.

 Pelvic examination will be done with each dose and with the onset of uterine contractions.
 Doses will be stopped with the onset of uterine contractions or when the maximum doses
 reached.

 After documentation of all the collected data, the following will be studied:

 -  Induction to onset of labor time.

 -  Induction to delivery time.

 -  Failure of induction due to maternal or fetal cause.

 -  Need for augmentation of labor by oxytocin.

 -  Recording any maternal or fetal morbidities.

 Possible Risk:

 Risks of induction of labor as failure of induction or maternal or fetal morbidities.

 Side effects of the used drugs. Complications of PROM either maternal or fetal.
Inclusion Criteria:

 -  Singleton pregnancy.

 -  Cephalic presentation.

 -  Bishop score < or = 6.

 -  Average size of the fetus.

 -  Adequate pelvic dimensions.

 -  Prelabour rupture of membranes.

 -  Term or post-term pregnancies with an indication for labor induction either maternal
 or fetal.

 Exclusion Criteria:

 -  Previous uterine scar (e.g. caesarian delivery or unknown uterine incision , previous
 hysterotomy or myomectomy of the uterine corpus involving entry of the uterine cavity
 or extensive myometrial dissection, previous uterine rupture)

 -  Patients with regular uterine contractions.

 -  Malpresentation.

 -  Multifetal gesta1tion.

 -  Established fetal distress ( e.g. thick meconium stained liguor or non reassuring CTG
 changes)

 -  Indication for CS, e.g. Major degree of cephalopelvic disproportion and fetal
 macrosomia.

 -  Placenta previa or vasa previa.

 -  Active genital herpes infection.

 -  Severe maternal illness (e.g. severe preeclampsia).

 -  Laboratory and clinical sign of chorioamnionitis.