The Effect of Nitroglycerin on the Intrauterine Device (IUD) Insertion Experience in Nulliparous Women
Condition: Contraception; Pain
Study type: Interventional

Summary: 
      Increasing ease of access of long-acting birth control methods, like intrauterine devices
      (IUDs), is an important way to reduce the risk of unintended pregnancy. Unfortunately, fear
      of IUD insertion in women who have not had children is common among health care providers and
      women alike, and this limits IUD use. To increase acceptance of this highly effective birth
      control method, there is a need to explore new, low cost, and easily applied methods to
      improve the insertion experience. This is a pilot study to evaluate the effectiveness and
      acceptability of nitroglycerin ointment applied vaginally to improve the IUD insertion
      experience for both patient and provider. The investigators hypothesis is that nitroglycerin
      ointment will decrease the pain associated with IUD insertion.
    

Detailed description: 
      Increasing acceptability and use of long acting reversible contraceptive methods like the
      intrauterine device (IUD) is an important strategy to reduce the risk of unintended
      pregnancy. Unfortunately, fear of IUD insertion in nulliparous women is common among health
      care providers and women alike, and this limits IUD use. While many health care providers
      assume that placement is more difficult in nulliparous women, there is no evidence that the
      risk of unsuccessful insertion is higher. Women worry about pain with insertion, and their
      fear is not unfounded as U.S. and international data have shown that nulliparous women report
      approximately twice as much pain with IUD insertion compared to parous women.

      A key difference between nulliparous and multiparous women is the resistance of the cervix.
      While cervical dilation is uncommonly needed during IUD placement, force is often required to
      pass the insertion device through the internal os. Although misoprostol and ibuprofen have
      been studied as ways to improve the IUD insertion experience, neither has proved effective,
      and misoprostol actually has been shown to increase pain. Therefore, to increase acceptance
      of this highly effective contraceptive, there is a need to investigate novel, low cost,
      easily applied and accessible techniques to improve the insertion experience.

      Nitric oxide (NO) donors, including nitroglycerin, nitroprusside, isosorbide mononitrate and
      isosorbide dinitrate, have effects on the animal and human cervix. Both nitroglycerin and
      isosorbide mononitrate tablets administered vaginally have been shown in RCTs to induce
      effective cervical ripening with minimal side effects for first trimester abortion compared
      to placebo. Nitroprusside and isosorbide dinitrate gel given intracervically prior to first
      trimester abortion also have showed minimal side effects in several RCTs, but with mixed
      results regarding effectiveness. Additional safety data about NO donors applied topically to
      skin and mucosal surfaces is well established through the routine use of topical
      nitroglycerin for treatment of anal fissures.

      Although a recent randomized controlled trial (RCT) comparing nitroprusside gel to
      misoprostol for cervical ripening prior to first trimester surgical abortion found superior
      cervical dilation in the misoprostol group, there was no significant difference in cervical
      dilation up to 5 mm. While most studies of abortion are concerned with providing adequate
      dilation beyond 8 mm, the cervical remodeling that is necessary to help with IUD insertion is
      much less, as the levonorgestrel intrauterine system (LNG-IUS) inserter is only 4.75 mm in
      diameter. Since NO donors are smooth muscle relaxants, they are expected to induce cervical
      ripening without causing uterine cramping, which is the most significant side effect of
      misoprostol.

      Nitroglycerin is inexpensive, stable at room temperature, and readily available in tablet and
      ointment form, as well as in a dextrose solution for intravenous administration. The ointment
      form is commonly applied topically for the treatment of anal fissures. We propose the
      following aims:

        1. To determine if nitroglycerin ointment applied vaginally 30-45 minutes prior to IUD
           insertion improves pain among nulliparous women compared to a placebo ointment.
           Self-reported pain scores on a 100 mm VAS will be assessed at multiple time points
           during and after the IUD insertion procedure. In addition, overall satisfaction and
           adverse effects will be evaluated.

        2. To determine if nitroglycerin ointment applied vaginally 30-45 minutes prior to IUD
           insertion improves ease of IUD insertion for the provider compared to a placebo
           ointment. In addition, need for additional dilation, additional pain medicine such as
           paracervical block, inability to place the IUD, and complications will be tracked.

        3. To determine if nitroglycerin ointment applied vaginally 30-45 minutes prior to IUD
           insertion is safe and well tolerated. Side effects related to treatment with
           nitroglycerin ointment or placebo will be compared. Blood pressure will be measured at
           multiple time points.
    

Intervention name(s): Insertion of nitroglycerin ointment; Insertion of placebo ointment
Intervention type(s): Drug; Drug
Intervention description(s): Nitroglycerin ointment inserted into the vagina 30-45 minutes prior to IUD insertion; Placebo ointment inserted into the vagina 30-45 minutes prior to IUD insertion
Intervention MeSH terms: Nitroglycerin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Intrauterine device; Pain; Contraception; Nitroglycerin; Nitric oxide donor; Intrauterine device insertion