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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 35  |  Issue : 1  |  Page : 104-110

Sublingual misoprostol before insertion of an intrauterine device


1 Department of Obstetrics and Gynecology, Faculty of Medicine, Benha University, Benha, Egypt
2 Department of Obstetrics and Gynecology, Ministry of Health, Benha, Egypt

Date of Submission15-Apr-2017
Date of Acceptance22-May-2017
Date of Web Publication28-Feb-2018

Correspondence Address:
Ahmed I Zaky Nada
Shebeen Elkom, Menoufya, 13511
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bmfj.bmfj_72_17

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  Abstract 


Objective The aim of the work was to investigate whether sublingual misoprostol before intrauterine contraceptive device (IUCD) insertion facilitates the insertion and reduces the number of failed insertions, insertion-related complications, and pain during insertion.
Background The intrauterine device (IUD) is a highly effective and safe contraceptive method. However, insertion through a narrow cervix may be technically difficult and painful. Misoprostol has been shown to be effective for cervical priming in nonpregnant women.
Patients and methods Two hundred and sixty women were randomly allocated to receive 400 mg misoprostol sublingually or placebo 2 h before IUD insertion. Primary outcome measure was the proportion of failed insertions. Pain during insertion and difficulty in IUCD insertion were evaluated. Complications and side effects were recorded together with bleeding and expulsion of the loop after 6 weeks.
Results Misoprostol significantly reduced the number of failed insertions from six failed insertion in the placebo group (4.6%) to only one (0.8%) case in the misoprostol group (P=0.023). Pain during insertion was significantly lower (P<0.001). Difficulty in insertion was significantly lower (P<0.001). As regards side effects, no significant differences were found between the two groups except for abdominal cramps and nausea. Cramps occurred in 22.3% of participants using misoprostol and in 5.4% of participants using placebo (P<0.001). Nausea occurred in 6.9% of participants using misoprostol and in 1.5% of participants using placebo (P=0.046). There were no significant differences as regards the rate of expulsion and the amount of vaginal bleeding.
Conclusion 400 micrograms of sublingual misoprostol 2 h before IUCD insertion reduces the number of failed insertions and pain during insertion. A facilitating effect of misoprostol on IUD insertion was also found.

Keywords: cervical priming, intrauterine device, misoprostol, sublingual


How to cite this article:
Mohammed MA, Seleem KS, Sadek AM, Zaky Nada AI. Sublingual misoprostol before insertion of an intrauterine device. Benha Med J 2018;35:104-10

How to cite this URL:
Mohammed MA, Seleem KS, Sadek AM, Zaky Nada AI. Sublingual misoprostol before insertion of an intrauterine device. Benha Med J [serial online] 2018 [cited 2018 May 23];35:104-10. Available from: http://www.bmfj.eg.net/text.asp?2018/35/1/104/226423




  Introduction Top


Intrauterine contraception (IUC) is the most widely used method of reversible fertility regulation in the world. Over 100 millions of women worldwide use it for contraception. In Cuba, Egypt, and North Korea, intrauterine contraceptive device (IUCD) use accounts for more than 50% of contraceptive use [1]. They have the highest rate of satisfaction and continuation of all reversible contraceptives [2].

Cervical stenosis, an immature or small cervix, and a significantly anteverted or retroverted position of the uterus has been described as factors associated with a difficult sounding of the cervical canal or even failure to insert the IUCD [3]. The mechanical means to overcome anatomic cervical stenosis and scarring during IUCD insertion are through direct cervical traction with a tenaculum and the additional use of a probe or dilator. These techniques are usually associated with increased pain, anxiety, or even failure [4]. Many women may feel discomfort or pain during and immediately after insertion of an IUCD. The fear of painful insertion may make women hesitate to use an IUCD [5]. Moreover, insertion failures and cervical problems seem to occur more often among women who have never delivered vaginally [4],[6]. Therefore, healthcare personnel may be reluctant to insert an IUCD as this procedure is perceived as risky, with potential complications including failure of insertion and perforation [7].

Misoprostol is an inexpensive prostaglandin E1-analog, which is associated with few side effects [8],[9]. Several studies have shown the benefit of misoprostol as a cervical ripening agent in nonpregnant women [3],[10],[11],[12],[13]. Sublingual administration is a more preferable and acceptable method to give misoprostol compared with the vaginal route. It can avoid the uncomfortable vaginal examination and provide more privacy [14]. Sublingual administration of misoprostol has been shown to be more effective also for cervical priming compared with oral administration [15] and equally effective as vaginal administration [14]. Another advantage is that the absorption of the drug is not affected if the women started to bleed and has less variation in absorption compared with the vaginal route [16]. This may be attributed to the variation between women in the amount and pH of the vaginal discharge [17].

The objective of this study was to determine whether or not sublingual misoprostol administered before IUCD insertion reduces the number of failed insertion, insertion-related complications, and pain.


  Patients and methods Top


Study design

The study design was a double-blinded placebo randomized controlled clinical one. This study was carried out in Faculty of Medicine, Benha University Hospitals after obtaining approval from the Ethics Research Committee.

Setting

The study was conducted in Benha University Hospital and other contraceptive centers that belong to ministry of health.

Time

The study was conducted during the period from October 2014 to September 2016.

Sample size calculation

Using Stata (2001; StataCorp., Texas, USA) the sample size was calculated on the basis of the primary outcome of failed insertion by setting a type 1 error of 0.05 and a power of 0.80. We aimed to detect a significant difference of expected failed insertions of 1.3% (the misoprostol group) versus 8.8% (the placebo group). The calculated sample size was, therefore, 260 patients. The power of the study to detect a 30% increase in side effects was 0.44.

Population of study

About 260 women candidate for copper T 380A IUCD insertion were enrolled in the study. About half of them received 400 mg of misoprostol sublingually and the other half received placebo.

Methods of randomization

To ensure that everyone has an equal chance of participation, randomization was guided by a table of random numbers. Double-blinded technique was used; thus, the investigator and the patient were not aware whether a patient received the drug or the placebo. Placebo and the drug were put in 260 numbered closed envelopes according to the table of random numbers and an envelope was allocated to each patient accordingly.

The study was conducted in a double-blinded manner: neither the doctor nor the participant knew whether placebo or misoprostol was administered. The randomization list was kept concealed from the investigators until the study was completed, to ensure a concealed allocation.

Inclusion criteria

Women above 18 years of age who were willing to undergo insertion of an IUCD and to participate in this research, women who delivered either vaginally or by cesarean section, and those with negative pregnancy test were included in the study.

Exclusion criteria

  • Positive pregnancy test.
  • Allergy to prostaglandin.
  • Allergy to copper.
  • Suggested gynecologic malignancy.
  • Uterine or cervical fibroid.
  • Pelvic inflammatory disease or cervical infection.
  • Unexplained vaginal bleeding.
  • Cervical or uterine anomaly.


Methodology

Written consent was taken from all women who were willing to participate, after providing a detailed explanation on the procedure, possible side effects, and complications.

Participants were randomly allocated to either the misoprostol or the placebo group.

Full personal, obstetric, menstrual, and medical history was taken. History of allergy to misoprostol was asked about. IUCD was inserted from the third to the fifth day of the menstrual cycle.

Pregnancy test was performed and those with a positive test were excluded. Abdominal and vaginal examination was carried out to exclude genital infections or masses.

Ultrasound examination was carried out to detect uterine position, whether anteverted or retroverted, uterine pathology, and uterine anomaly. A bimanual examination and sounding of the uterus before insertion are necessary to determine the position and depth of uterine cavity.

All women received a numbered, blinded packet with either two tablets of misoprostol or two tablets of placebo. Women took the tablets sublingually 2 h before loop insertion.

Study outcome measures

The primary outcome measure of this study was the proportion of failed IUCD insertions, defined as an unsuccessful insertion, regardless of the reason (e.g. immediate expulsion or impossibility to sound the uterus). Pain during insertion and difficulty of IUCD insertion were estimated. Pain was measured using a visual analog scale graded from 0 to 10 to represent the continuum of ‘no pain’ to ‘worst imaginable pain’. Difficulty of IUCD insertion was measured using a five-point scale. Uterine or cervical perforation, heavy bleeding, vasovagal-like reactions (dizziness, nausea, and vomiting), syncope, and partial or total expulsion were also recorded. Both the participant and the clinician filled out the scale directly after the insertion procedure.

Side effects of misoprostol or placebo were also scored by the participant. Hereby, a box was ticked per side effect, ranging from mild, moderate, to severe. The side effects queried were headache, nausea, vomiting, abdominal cramping, shivering, fever, and diarrhea. The participant filled out this side effect form before intrauterine device (IUD) insertion was performed to ensure that side effects from medication or placebo were not mistaken for side effects related to insertion.

The patient was asked to keep daily records of bleeding until the time of follow-up visit. The amount of blood loss was estimated using the pictorial blood loss assessment chart. The chart takes into account the degree to which each item of sanitary protection is soiled with blood as well as the number used. Scores are assigned to different degrees of soiling pads. The scores assigned will be 1 for each lightly stained tampon, 5 if moderately soiled, and 10 if was completely saturated with blood. The towels were given ascending scores 1, 5, and 10. Small and large clots were scored between 1 and 5, respectively. Patients were asked to return for a follow-up visit after 6 weeks. Examination or ultrasound was performed to assess IUCD expulsion. In addition, the records for bleeding were collected.

Statistical analysis

The collected data were tabulated and analyzed using SPSS software (SPSS; SPSS Inc., Chicago, Illinois, USA). Continuous variables were presented as mean±SD. Categorical variables were expressed as number and percentage. Suitable tests of significance were calculated. The accepted level of significance in this work will be 0.05.


  Results Top


The study showed no statistically significant difference between the two groups as regards the baseline demographic data such as age, parity, and BMI. Moreover, there was no significant difference as regards uterine length and position. However, there was a significant difference as regards the degree of difficulty of uterine sounding, being easier in the misoprostol group ([Table 1]).
Table 1 Comparison between the misoprostol group and the placebo group as regards baseline demographic data such as age, parity, and BMI, as well as uterine length and position and difficulty of uterine sounding group

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The study showed that pretreatment with misoprostol significantly reduced the number of failed insertions from six (4.6%) failed insertion in the placebo group to only one (0.8%) case of failed insertion in the misoprostol group. Moreover, pain during insertion was improved and was significantly lower with misoprostol [12 (9.2%) patients experienced moderate and severe pain in the misoprostol group compared with 47 (36.2%) patients in the placebo group]. Difficulty in insertion was estimated with regard to the resistance of the cervix. A facilitating effect of misoprostol on IUD insertion was found, with significantly less resistance of the internal cervical os and technically less difficult insertions compared with the untreated controls ([Table 2]).
Table 2 Comparison between the misoprostol group and the placebo group as regards the fate of insertion of intrauterine contraceptive device, difficulty in insertion, and pain during insertion

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The overall number of major complications was low and insignificant. As regards side effects, there were no statistically significant differences between the two groups except for abdominal cramps and nausea. Abdominal cramps occurred in 22.3% of participants using misoprostol and in 5.4% using placebo. Nausea occurred in 6.9% of participants using misoprostol and in 1.5% using placebo ([Table 3]).
Table 3 Comparison between group I and group II as regards complications and medication-related side effects

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There were no significant differences between the two groups as regards the rate of expulsion of the loop and the amount of vaginal bleeding after 6 weeks ([Table 4]).
Table 4 Location of intrauterine contraceptive device after 6 weeks of follow-up and bleeding during 6 weeks follow-up using pictorial blood loss chart

Click here to view



  Discussion Top


Our study was conducted to assess whether or not 400 μg of sublingual misoprostol administered 2 h before IUCD reduces the number of failed insertions and insertion-related complications. It included 260 women in each group. One group received 400 mg of sublingual misoprostol 2 h before IUCD insertion and the other received the placebo. This study showed a positive effect of administration of misoprostol. Misoprostol significantly reduced the number of failed insertions from six (4.6%) failed insertion in the placebo group to only one (0.8%) case in the misoprostol group (P=0.023). Pain during insertion was improved and significantly lower (P<0.001). Twelve (9.2%) patients experienced moderate and severe pain in the misoprostol group compared with 47 (36.2%) patients in the placebo group. Difficulty in insertion was significantly lower (P<0.001). As regards side effects, no significant differences were found between the two groups except for abdominal cramps and nausea. Cramps occurred in 22.3% of participants using misoprostol and in 5.4% using placebo (P<0.001). Nausea occurred in 6.9% with misoprostol and in 1.5% with placebo (P=0.046). No significant differences were found as regards the rate of expulsion and the amount of vaginal bleeding.

The present findings are in agreement with the results published by other authors with respect to the degree of difficulty and reduction of pain during insertion [4],[5],[18],[19],[20],[21],[22].

Ahmed et al. [18] found that 400 mg of sublingual misoprostol 1 h before IUCD insertion facilitates the procedure and can provide an easier and more successful insertion of the device but did not decrease pain during insertion. In another study that included 140 patients randomized to the misoprostol and placebo groups, Abdullah et al. [19] found that 400 mcg of vaginal misoprostol 3 h before insertion increases the success rate of insertion [69 (98.6%) vs. 61 (87.1%), P=0.009]. Pain and difficulty in insertion were also reduced.

Bahamondes et al. [20] also tried the pretreatment with 200 mcg of intravaginal misoprostol 10 and 4 h before IUCD insertion in patients with a history of failure to insert the loop during the first trial. He found that insertion failure was significantly better than that in the placebo group. The IUCD was successfully placed in 42 (87.5%) women of the 48 women and in 26 (61.9%) of the 42 women randomized to misoprostol and placebo, respectively (P=0.0066). Relative risk of successful insertions was 1.41 (95% confidence interval for absolute difference (8.2–43.0) [20].

The results of an RCT with sublingual misoprostol 1 h before insertion of a copper-IUD among nulliparous women were published [5]. Eighty women requesting an IUD were randomly allocated to sublingually receive 400 mg misoprostol and 100 mg diclofenac (the misoprostol group) or 100 mg diclofenac alone (the control group) 1 h before IUD insertion. Following treatment with misoprostol, insertion was significantly easier than that in the control group (P=0.039, difference 19.36%, confidence interval: 20.013–39.99). Pain estimated on a visual analogue scale showed no evidence of a difference between the groups. There were very few failures to insert the IUD, only two insertions failed due to very narrow cervix in the control group and none of the insertions failed in the misoprostol group. The overall distribution of side effects did not differ. However, shivering was more common in the misoprostol group. Overall, there was no evidence of a difference between the groups in the distribution of side effects reported. Pain and bleeding during the first month after insertion were also comparable between the groups and showed no evidence of a difference.

Scavuzzi et al. [21] also reported that the use of misoprostol at a dose of 400 mg administered vaginally 4 h before IUCD insertion increased the ease of insertion and reduced the pain during the procedure, although the frequency of cramps increased. Women were randomly allocated to two groups: 86 to receive misoprostol vaginally and 93 to receive placebo. Significant differences were found, with less difficulty in inserting the IUD, a lower risk for dilatation, a reduction in moderate-to-severe pain at IUD insertion and a lesser likelihood of experiencing a disagreeable or very disagreeable sensation in the group that was given misoprostol compared with the group that received placebo. There was no significant difference between the groups in relation to complications during IUD insertion. There were no cases of uterine perforation in either group. The frequency of cramps was 40% higher in the misoprostol group. No significant differences were found between the two groups when the frequency of heavy menstrual bleeding, intermenstrual bleeding, spotting, cramps, Pelvic inflammatory disease (PID), or expulsion rates were compared [21].

In another study involving a small series of cases (eight cases) in which insertion failed due to cervical stenosis, the use of 400 mg of misoprostol vaginally resulted in successful insertion in all women involved, suggesting a greater ease of insertion of the IUD with the previous use of misoprostol [4].

One study recently published in the USA evaluated the opinion of 2211 physicians working in the field of reproductive medicine. Overall, 1905 (86%) individuals interviewed reported inserting IUCDs in nulligravidas, and, of these, 947 (42.7%) had used misoprostol before the procedure, with the majority (n=515; 54%) believing that the use of this medication greatly facilitates insertion of the device [22].

However, some studies failed to find any reduction in pain during the procedure and found no increase in the likelihood of insertion being successful [23],[24],[25],[26],[27].

However, Lotke et al. [23] stated that routine use of misoprostol before intrauterine device insertion is not warranted. The results of their study that included a small number of patients (31 participants in the placebo group and 30 receiving misoprostol) who had a positive point for the use of misoprostol reported easier insertions following misoprostol (24.1±14.2 mm misoprostol vs. 33.4±20.3 mm placebo, P=0.04). All patients had successful IUD placement and none had complications. This may be due to the small number of patients. There was no difference in baseline pain, and no difference in pain immediately after IUD insertion (57.2±22.5 mm for placebo, 56.7±22.1 mm for misoprostol, P=0.92). Patients receiving misoprostol experienced more cramps (16.7% placebo, 60% misoprostol, P=0.002). Fever and chills were also reported, although this did not reach significance (7% placebo and 27% misoprostol, P=0.081) [23].

Dijkhuizen et al. [24] conducted a RCT on about 270 patients, aiming to investigate whether pretreatment with vaginal misoprostol facilitates the insertion of an IUD in nulliparous and multiparous women and showed no benefit for use of misoprostol before IUD insertion. However, there is a tendency of possible harm as regards side effects [24].

A recently published clinical trial in which 400 mg of misoprostol was used orally 90 min before IUD insertion in 35 nulligravidas found no significant difference in the pain reported by the women. In that study, a greater frequency of side effects, particularly cramps and nausea, was found in the misoprostol group [25].

Heikinheimo et al. [26] published the results of a double-blind RCT in which 43 women used sublingual 400 mg misoprostol and 46 women used a placebo 3 h before an immediate replacement of a second LNG-IUD. No significant effect on the ease of insertion or on the patient-reported pain was seen. However, significantly more side effects were observed in the misoprostol than in the placebo group. This may be due to the small number of participants in their study and the use of sublingual route with 3-h interval as sublingual misoprostol is more effective after 1 h [26].

This study showed a positive effect of administration of misoprostol. The benefits of this drug can outweigh the side effects presented.


  Conclusion Top


The use of 400 mg of sublingual misoprostol administered 2 h before IUCD insertion reduces the number of failed insertions and reduces pain during insertion. A facilitating effect of misoprostol on IUD insertion was also found.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Population Reports (2007): Intrauterine Devices. Series B, Number 7; Baltimore (MD): INFO Project, Center for Communication Programs, the Johns Hopkins Bloomberg School of Public Health. Available at: http://www.infforhealth.org. [Last accessed 2016 Nov].  Back to cited text no. 1
    
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Preutthipan S, Herabutya Y. A randomized comparison of vaginal misoprostol and dinoprostone for cervical priming in nulliparous women before operative hysteroscopy. Fertil Steril 2006; 86:990–994.  Back to cited text no. 3
    
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Sääv I, Aronsson A, Marions L, Stephansson O, Gemzell-Danielsson K Cervical priming with sublingual misoprostol prior to insetion of an intrauterine device in nulliparous women: arandomised controlled trial. Hum Reprod 2007; 22:2647–2652.  Back to cited text no. 5
    
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Farmer M, Webb A. Intrauterine device insertion related complications: can they be predicted? J Fam Plann Reprod Health Care 2003; 29:227.  Back to cited text no. 6
    
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Ahmed MY, Bayoumy HA, Sweed MS. (2016) sublingual misoprostol prior to IUD insertion in women with only previous caesarian section: Thesis of master degree in Faculty of Medicine Ain Shams University. 48–53. June with 559 Reads. doi: 10.1016/j.contraception.2017.01.003.  Back to cited text no. 18
    
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20.
Bahamondes MV, Espejo-Arce X, Bahamondes L. Effect of vaginal administration of misoprostol before intrauterine contraceptive insertion following previous insertion failure: a double blind RCT. Hum Reprod 2015; 30:1861–1866.  Back to cited text no. 20
    
21.
Scavuzzi A, Souza1 AS, Costa AA, Amorim MM Misoprostol prior to inserting an intrauterine device in nulligravidas: a randomized clinical trial. Hum Reprod 2013; 28:2118–2125.  Back to cited text no. 21
    
22.
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24.
Dijkhuizen K, Dekkers OM, Holleboom CA, de Groot CJ, Hellebrekers BW, van Roosmalen GJ et al. Vaginal misoprostol prior to insertion of an intrauterine device: an RCT. Hum Reprod 2011; 26:323–329.  Back to cited text no. 24
    
25.
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26.
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27.
Espey E, Singh RH, Leeman L, Ogburn T, Fowler K, greeneces H. Misoprostol for intrauterine device insertion in nulliparous women: a randomized controlled trial? Am J Obstet Gynecol 2014; 210:208.e1–208.e5.  Back to cited text no. 27
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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