Vaginal Misoprostol Prior to Insertion of an IUD
Background: Misoprostol is an agent that may ripen the cervix in nonpregnant women. Here, we investigate whether vaginal misoprostol administered prior to intrauterine device (IUD) insertion reduces the number of failed insertions, insertion-related complications and pain during insertion.
Methods: We conducted a double-blinded, multicenter randomized controlled trial among patients requesting an IUD. Nulli- and multi-parous women were included, and both copper-containing and levonorgestrel-releasing IUDs were used. Participants were allocated to either 400 μg misoprostol or placebo (administered 3h prior to IUD insertion). The primary outcome measure was failed insertion. Secondary outcome measures were insertion-related complications, pain, difficulty of insertion and side-effects.
Results: Two hundred and seventy participants were randomized. After drop out for various reasons (mainly no show), 199 participants had an IUD inserted; 102 received misoprostol and 97 received placebo. Only three insertions failed; two in the misoprostol group and one in the placebo group [P = 0.59, relative risk (RR) 1.9, 95% confidence interval (CI) 0.2–20.6]. The overall incidence of insertion-related complications was 21.8% in the misoprostol versus 19.1% in the placebo group (mainly vasovagal-like reactions) and did not differ between groups (P = 0.65, RR 1.1, 95% CI 0.7–2.0). No difference in pain scores between groups was found. Side-effects were more common in the misoprostol group (P = 0.05, RR 1.3, 95% CI 1.0–1.7).
Conclusion: The study showed no benefit for use of misoprostol prior to IUD insertion. However, there is a tendency of possible harm regarding side-effects. Therefore, we would not recommend standard pretreatment with misoprostol.
Intrauterine devices (IUDs) are widely used as reversible contraceptives. Both copper- and levonorgestrel (LNG)-releasing IUDs (LNG-IUDs) are safe, cost-effective in the long term and equally effective compared with tubal sterilization (Grimes et al., 2007; Grimes and Mishell, 2008). In addition, the LNG-IUD (Mirena®) provides noncontraceptive benefits, such as treatment for menorrhagia, dysmenorrhea and anemia (Luukkainen and Toivonen, 1995; Hurskainen et al., 2004; Milsom, 2007). The current use of IUDs among reproductive-aged women ranges from 8 to 15% worldwide (D'Arcangues, 2007). In the Netherlands, the use of IUDs among women aged 18–45 years has increased from 3 to 8% over the last 10 years (CBS, 2008).
Reported complications related to IUD insertion are: 8.8% insertion failure, 2.8–11.5% cervical problems, 0.2% cervical perforation, 0.2% syncope and 5.8% expulsion (Farmer and Webb, 2003). Insertion failures and cervical problems seem to occur more often among women who have never delivered vaginally (Farmer and Webb, 2003; Li et al., 2005). Cervical stenosis, an immature or small cervix and a significantly ante- 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 IUD (Preutthipan and Herabutya, 2006). The use of prophylactic nonsteroidal anti-inflammatory drugs (NSAIDs) prior to IUD insertion has been advocated to reduce pain during insertion (Jensen et al., 1998; Sääv et al., 2007) and has been common practice in the Netherlands for years. However, in a large randomized controlled trial (RCT) comparing prophylactic 400 mg ibuprofen with placebo prior to IUD insertion, no pain reduction was shown (Hubacher et al., 2006).
Misoprostol is an inexpensive prostaglandin E1-analogue, which is associated with few side-effects (Goldberg et al., 2001; Wing and Gaffaney, 2006) and an effective method for treatment of missed and incomplete abortion, induction of provocative abortion as well as for labor induction and prevention and treatment of postpartum hemorrhage (Ngai et al., 1999; Goldberg et al., 2001). Moreover, several studies have shown the benefit of misoprostol as a cervical ripening agent in nonpregnant women (Ngai et al., 1997; Singh and Fong, 2000; Barcaite et al., 2005; Oppegaard et al., 2006; Preutthipan and Herabutya, 2006). Priming with misoprostol prior to hysteroscopy and dilatation and curettage (D&C) in premenopausal women resulted in an increased cervical dilatation and a lower rate of cervical laceration (Crane and Healey, 2006; Preutthipan and Herabutya, 2006). A single dose of 400 μg misoprostol given vaginally 3h before the intervention has given the best effectiveness with the least side-effects. Higher doses or longer intervals do not improve the effect on the cervix, whereas higher doses actually increase side-effects (Singh and Fong, 2000; Fiala et al., 2007).
Given the benefits of misoprostol prior to hysteroscopy, we hypothesized that administering a cervical ripening agent prior to IUD insertion would reduce failure rates, complications and pain during insertion.
A study among eight women with an initially failed IUD insertion showed that a second attempt, after pretreatment with misoprostol, was successful in all eight cases (Li et al., 2005). However, larger studies on the effect of misoprostol for IUD insertion are lacking. We therefore conducted a RCT aiming to investigate whether pretreatment with misoprostol facilitates the insertion of an IUD in nulli- and (multi)parous women.
Abstract and Introduction
Abstract
Background: Misoprostol is an agent that may ripen the cervix in nonpregnant women. Here, we investigate whether vaginal misoprostol administered prior to intrauterine device (IUD) insertion reduces the number of failed insertions, insertion-related complications and pain during insertion.
Methods: We conducted a double-blinded, multicenter randomized controlled trial among patients requesting an IUD. Nulli- and multi-parous women were included, and both copper-containing and levonorgestrel-releasing IUDs were used. Participants were allocated to either 400 μg misoprostol or placebo (administered 3h prior to IUD insertion). The primary outcome measure was failed insertion. Secondary outcome measures were insertion-related complications, pain, difficulty of insertion and side-effects.
Results: Two hundred and seventy participants were randomized. After drop out for various reasons (mainly no show), 199 participants had an IUD inserted; 102 received misoprostol and 97 received placebo. Only three insertions failed; two in the misoprostol group and one in the placebo group [P = 0.59, relative risk (RR) 1.9, 95% confidence interval (CI) 0.2–20.6]. The overall incidence of insertion-related complications was 21.8% in the misoprostol versus 19.1% in the placebo group (mainly vasovagal-like reactions) and did not differ between groups (P = 0.65, RR 1.1, 95% CI 0.7–2.0). No difference in pain scores between groups was found. Side-effects were more common in the misoprostol group (P = 0.05, RR 1.3, 95% CI 1.0–1.7).
Conclusion: The study showed no benefit for use of misoprostol prior to IUD insertion. However, there is a tendency of possible harm regarding side-effects. Therefore, we would not recommend standard pretreatment with misoprostol.
Introduction
Intrauterine devices (IUDs) are widely used as reversible contraceptives. Both copper- and levonorgestrel (LNG)-releasing IUDs (LNG-IUDs) are safe, cost-effective in the long term and equally effective compared with tubal sterilization (Grimes et al., 2007; Grimes and Mishell, 2008). In addition, the LNG-IUD (Mirena®) provides noncontraceptive benefits, such as treatment for menorrhagia, dysmenorrhea and anemia (Luukkainen and Toivonen, 1995; Hurskainen et al., 2004; Milsom, 2007). The current use of IUDs among reproductive-aged women ranges from 8 to 15% worldwide (D'Arcangues, 2007). In the Netherlands, the use of IUDs among women aged 18–45 years has increased from 3 to 8% over the last 10 years (CBS, 2008).
Reported complications related to IUD insertion are: 8.8% insertion failure, 2.8–11.5% cervical problems, 0.2% cervical perforation, 0.2% syncope and 5.8% expulsion (Farmer and Webb, 2003). Insertion failures and cervical problems seem to occur more often among women who have never delivered vaginally (Farmer and Webb, 2003; Li et al., 2005). Cervical stenosis, an immature or small cervix and a significantly ante- 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 IUD (Preutthipan and Herabutya, 2006). The use of prophylactic nonsteroidal anti-inflammatory drugs (NSAIDs) prior to IUD insertion has been advocated to reduce pain during insertion (Jensen et al., 1998; Sääv et al., 2007) and has been common practice in the Netherlands for years. However, in a large randomized controlled trial (RCT) comparing prophylactic 400 mg ibuprofen with placebo prior to IUD insertion, no pain reduction was shown (Hubacher et al., 2006).
Misoprostol is an inexpensive prostaglandin E1-analogue, which is associated with few side-effects (Goldberg et al., 2001; Wing and Gaffaney, 2006) and an effective method for treatment of missed and incomplete abortion, induction of provocative abortion as well as for labor induction and prevention and treatment of postpartum hemorrhage (Ngai et al., 1999; Goldberg et al., 2001). Moreover, several studies have shown the benefit of misoprostol as a cervical ripening agent in nonpregnant women (Ngai et al., 1997; Singh and Fong, 2000; Barcaite et al., 2005; Oppegaard et al., 2006; Preutthipan and Herabutya, 2006). Priming with misoprostol prior to hysteroscopy and dilatation and curettage (D&C) in premenopausal women resulted in an increased cervical dilatation and a lower rate of cervical laceration (Crane and Healey, 2006; Preutthipan and Herabutya, 2006). A single dose of 400 μg misoprostol given vaginally 3h before the intervention has given the best effectiveness with the least side-effects. Higher doses or longer intervals do not improve the effect on the cervix, whereas higher doses actually increase side-effects (Singh and Fong, 2000; Fiala et al., 2007).
Given the benefits of misoprostol prior to hysteroscopy, we hypothesized that administering a cervical ripening agent prior to IUD insertion would reduce failure rates, complications and pain during insertion.
A study among eight women with an initially failed IUD insertion showed that a second attempt, after pretreatment with misoprostol, was successful in all eight cases (Li et al., 2005). However, larger studies on the effect of misoprostol for IUD insertion are lacking. We therefore conducted a RCT aiming to investigate whether pretreatment with misoprostol facilitates the insertion of an IUD in nulli- and (multi)parous women.