Summary

Journal of Rawalpindi Medical College (JRMC); 2010;14(2):101-103
Vaginal Isosorbide Mononitrate and Misoprostol for
Induction of Cervical Ripening Prior to 1st Trimester
Surgical Evacuation of Retained Products of
Conception
Uzma Shafique, Farzana Kazmi, Farah Rehana Department of Obstetrics and Gynaecology,DHQ Teaching Hospital Rawalpindi Abstract
However prostaglandins are associated with side effects such as nausea, vomiting, diarrhoea, abdominal cramps, chills, shivering and To compare the effect of vaginal
isosorbide mononitrate with misoprostol for cervical uterine hyperstimulation.3
ripening in women with first trimester missed abortion
Nitric oxide releasing drugs are the novel class before surgical evacuation of uterus.
of effective and safe drugs for cervical ripening.4,5 It Methods: In this randomized controlled trial, hundred has been shown to be a major paracrine mediator of
patients, requiring cervical ripening and surgical numerous biological processes including smooth
evacuation of retained products of conception, were
muscle relaxation, host defence and inflammation. 6 divided into two equal groups. Misoprostol (400 Cervical ripening is thus associated with changes in
microgram) was placed in posterior vaginal fornix in local cytokines, prostaglandins and metalloproteases
Group A patients and dose was repeated every three hours
as well as in other bioregulators that play role in upto 4 doses or until reaching cervical ripening. inflammation and in collagen metabolism.7 These
Isosorbide mononitrate (80milligram) was given vaginally
in Group B patients and dose was repeated every three
factors also take part in regulation of nitric oxide hours up to 4 doses or until reaching the cervical ripening.
synthesis and release. 8 Several chemical donors of Results: There was no significant difference in side nitric oxide are currently being used in various types
effects between two groups. However Misoprostol was
of experimental and therapeutic studies. 9 more effective than Isosorbide Mononitrate (IMN) to cause
cervical ripening before suction termination of first
Patients and Methods
trimester missed abortion .
Conclusion: Nitric oxide donor "Isosorbide
In this randomized controlled trial, all patients mononitrate" is less effective than "Misoprostol" to induce
admitted through OPD and emergency of Gynae / cervical ripening prior to first trimester surgical evacuation
of retained products of conception and both drugs are
Obstetrics unit of DHQ Teaching hospital, having associated with a high frequency of side effects.
ultrasound evidence of a gestation sac and a non- Key Words: Cervical Ripening, Missed abortion, nitric viable embryo requiring cervical ripening and surgical
oxide donor, misoprostol.
evacuation of retained products of conception, were included. Women with unexplained vaginal bleeding or discharge, with any contraindication to use of isosorbide mononitrate, cardiac disease or The uterine cervix has to be firm enough to hypersensitivity to the drug and cervical dilatation retain the conceptus through the pregnancy and on the more than 8mm were excluded from study. Vaginal other hand have the ability to soften before and during examination was carried out at the time of admission labour to enable the birth of infant. Cervical ripening to assess cervical ripening and maturation is very important pre-requisite for the Randomization was done (lottery method) and successful termination of pregnancy.1 double blind technique was applied to decrease Two major techniques for iatrogenic cervical observer bias and patient bias.In group A patient's ripening are mechanical intervention such as 400 micro gram of misoprostol was placed in posterior disruption of fetal membranes or insertion of dilators vaginal fornix every 3 hrs up to four doses or until and application of cervical ripening agent such as reaching cervical ripening. The maximum dose of Journal of Rawalpindi Medical College (JRMC); 2010;14(2):101-103
misoprostol was 1600 microgram. In group B patient's induction to ripening interval was significantly 80mg of isosorbide mononiterate was given vaginally (8.03±2.833 vs. 4.47±2.042, P-value < 0.05) higher in and dose was repeated every three hrs up to four IMN group as compared with Misoprostol group, doses or until reaching cervical ripening. The which is shown in Table 3. maximum dose of isosorbide mononitrate was 320mg. During this procedure vital signs, symptoms Table 1:Distribution of Doses in both Groups
and adverse effects were recorded at base line and Drug Group
then every 3 hrs until finishing therapy. Time of 1st, No. Of Doses
2nd, 3rd and 4th dose of tablet was noted and Misoprostol
induction – ripening interval was recorded. If cervical dilatation was more than or equal to 8mm, then surgical evacuation of retained products of conception Mean and standard deviations were calculated for quantitative variables i.e. induction-ripening interval, age, parity, duration of gestation and cervical score. Frequencies and percentages were calculated for Table 2: Induction to ripening interval
qualitative variables such as headache, abdominal Induction to
pain, pelvic pain, backache, nausea and vomiting. Drug Group
ripening
Frequency Percent
Independent sample t-test was used to compare interval
induction-ripening interval between isosorbide Misoprostol mononitrate and misoprostol. Chi-square test was used to compare the side effects. P value less than 0.05 was taken as significant. In isosorbide mononitrate (IMN) group the mean age was 27.52 ±5.168 years ranging from 18 to 40 years and in Misoprostol group the mean age was 28.26±5.244 years. The gestational age in both groups was almost same .The parity distribution showed that in IMN group 28% were primipara 52% were multi para and 20% were grand multi para. In Misoprostol group 10% were primipara, 82% were multipara and 8% were grand multipara. Table 3:Comparison of Induction to
Both the drugs were used as until the Ripening Interval (hours)
ripening, the frequency of doses was relatively higher in IMN group. The highest dose frequency that was Drug Group
used in Misoprostol group was 1. In 29 patients the Deviation
required level was achieved after 1 dose of Misoprostol but in the IMN group the highest frequency of doses used was 2 doses which were used in 19 patients followed by 4 doses which were used in In side effects profile headache was 17 patients as given in (Table 1). significantly high in IMN group than Misoprostol In Misoprostol group the interval with highest group (p-value 0.05). There was no significant frequency was 3 hours at which 30 (59%) patients difference in hypotension in both groups (p-value achieved the required level. This interval was <0.05). Abdominal pain was significantly higher in comparatively higher in IMN group in which the Misoprostol group as compared to IMN group (p- interval at which the required level was achieved was value<0.05) .The backache was same in both groups 6 hours (32%), followed by 9 hours (26%) as given in (p-value>0.05). The nausea was only observed in Table 2. The analysis of data showed that the mean Misoprostol group (p-value <0.05) that was Journal of Rawalpindi Medical College (JRMC); 2010;14(2):101-103
significantly higher as compared to IMN group. The uterine atony during surgery (p<0.05). In this study results also show that vomiting was higher in 80mg of IMN and 200microgram of Misoprostol Misoprostol group as compared to IMN group (Table vaginal gel was used to cause cervical ripening. 10 Conclusion
Table 4:Comparison of side effects
Side Effects
Misoprostol
1. Benefits of Misoprostol are greater than its side effects so it is a better cervical ripening agent prior to suction evacuation of first trimester missed abortion with acceptable side effects. 2. Use of Misoprostol for cervical ripening reduces the induction to ripening interval leading to early surgical evacuation and short hospital stay. Discussion
References
The present study showed that misoprostol 1. Mohyuddin S, Akhtar S, Shamsi A, Mustafa N, Jabbar T.Comparative study of extra amniotic prostaglandin F2 (400 microgram) induced a more rapid cervical and increasing intravenous oxytocin infusion for dilatation as compared to Isosorbide mononitrate termination of pregnancy. Pak Armed Forces Med J, 2005; (80mg). The induction - ripening interval was significantly higher in IMN group as compared to Maul H, Mackay L, Garfield RE.Cervical ripening: biochemical, molecular and clinical consideration. Clin Misoprostol group. In Misoprostol group the interval Obstet Gynecol , 2006; 49:551 with highest frequency was 3 hours at which 29(58%) Chanrachakul B, Herabutya Y, Punyavachira E. patients achieved required level. This interval was Randomized trial of isosorbide mononitrate versus misoprostol for cervical ripening at term. Int J Gynecol comparatively higher in IMN group in which the Obstet , 2002; 78: 139-45 interval at which required level was achieved was 6 Vaisanen J , Tommiska M, Nuutila Ml. Nitric oxide hours (32%) followed by 9 hours (26%). Similarly the metabolites in cervical fluids arising pregnancy: further evidence for role of cervical nitric oxide in cervical frequency of doses was relatively higher in IMN ripening. Am J Obstet Gynecol, 2003; 188: 779 – 85. group. The highest dose frequency, which was used in Arteaga-Troncoso G, Villegas-Alvarado A, Belmont-Gomez Misoprostol group, was 1 in 29 patients while in IMN A. Intracervical administration of nitric oxide donor group the highest dose frequency was 2 doses, which isosorbide dinitrate for induction of cervical ripening: a randomized controlled trial to determine clinical efficacy were used in 19 patients followed by 4 doses, which and safety prior to 1st trimester surgical evacuation of were used in 17 patients. The poor clinical response of retained products of conception. BJOG, 2005; 112: 1615 – IMN in above-mentioned study and in our study is difficult to explain. It is unlikely that dosage of IMN Korhonen R, Lahti A, Kankaanranta H, Moilanen E. Nitric oxide production and signaling in inflammation. Curr has any major effect as a higher dose of IMN (80mg) Drug Targets Inflamm Allergy, 2005; 4:471- gave the same ripening effects as 40mg of IMN. The side effects were more frequently seen in Sennstrom MB, Ekman G, Westergren-thorsson G. Human cervical ripening, an inflammatory process mediated by our study which may be due to the fact that we used cytokines. Mol Hum Reprod, 2000; 6:375-81 maximum 4 doses of each drug in our patients where Maul H, Longo M, Saade GR, Garfield RE. Nitric oxide and as in studies with less side effects single dose of each its role during pregnancy: from ovulation to delivery. Curr Pharm Des, 2003; 9:359-80. drug was used. Another study was published in 2008 David M, Chen FC. Comparison of isosorbide mononitrate on the side effects of vaginal application of IMN, and misoprostol for cervical ripening in 1st trimester Misoprostol and DILAPAN-S, a hygroscopic cervical missed abortion. Arch Gynecol Obstet, 2005; 273: 144 – dilator prior to first trimester curettage. This study 10. Chen FC, Bergann A, Krosse J, Merholz A, David showed that all patients indicated mild discomfort M.Isosorbidemononitrate vaginal gel versus misoprostol after DILAPAN where as no patient complained of vaginal gel versus Dilapan-s for cervical ripening before discomfort after Misoprostol or IMN (P<. 0001). 3 first trimester curettage. Eur J Obstet Gynecol Reprod Biol 2008; 138:176-79. patients suffered from mild hypotension and headache after IMN and 2 had increased vaginal bleeding due to

Source: http://www.journalrmc.com/volumes/1394532082.pdf