Optimizing Patient Analgesic Experience During IVF
Condition: Infertility
MeSH terms: Infertility
Study type: Interventional

Summary: 
      This study is for patients undergoing In Vitro Fertilization (IVF). The investigators are
      studying the best way to control pain during the egg retrieval process. The egg retrieval
      involves passing a needle under ultrasound guidance through the vagina into the ovaries to
      remove eggs that are to be later fertilized. Patients often report this as very
      uncomfortable.

      Different fertility clinics across the country use different methods of pain control. All
      clinics will use intravenous medication to control pain, while some may or may not use local
      anaesthetic (freezing) in the vagina. Our goal is to find the best way to control pain. Since
      local anaesthetic injection involves multiple needle punctures and may be painful, the
      investigators are unsure if local anaesthetic is necessary in addition to the intravenous
      pain medication.

      The investigators will conduct a randomized trial where all patients will receive intravenous
      pain medication, but some will receive local anaesthetic injection and some will receive
      placebo injection. Patients will be asked to complete a questionnaire on their pain
      experience after oocyte retrieval. The investigators will then analyze the data and determine
      whether local anaesthetic actually improves pain when patients are already receiving
      intravenous pain medications. Through our study, the investigators aim to improve the pain
      experience of all women undergoing IVF in the future.
    

Detailed description: 
      Background:

      A UK telephone survey (Bokhari, 1999) showed that during TUGOR, 48% of UK fertility centers
      were using conscious sedation, 29% general anaesthesia, 12% conscious sedation with regional
      anaesthesia (neuraxial block or PCB), and 2% regional anaesthesia alone. A review article
      (Blahos 2009) details the many different types of anaesthesia used during TUGOR. These may
      include combinations of the following: general anaesthesia, regional anaesthesia, local
      anaesthesia, conscious sedation, and alternative methods of anaesthesia (electro-acupuncture,
      patient controlled sedation). No recent studies were found detailing the frequency of each of
      the various anaesthetic options in use at fertility centers across North American.

      A prospective, randomized, double-blind and placebo controlled study (Ng, 1999) showed that
      paracervical block combined with conscious sedation was superior to conscious sedation alone.
      This study used a combination of drugs (mepiridine and diazepam) not used at our center. The
      use of fentanyl and midazolam was first described by Harrison in 1992 for conscious sedation.
      In 2001 Sephton et al published a cross over audit of patient preferences comparing
      mepiridine, diazepam and promethazine to fentanyl and midazolam, showing superiority of
      fentanyl and midazolam. Midazolam has sedative and amnestic properties, whereas diazepam has
      no amnestic properties. The amnestic properties of midazolam make it a superior medication
      for overall patient experience during TUGOR, as they are less likely to recall potentially
      painful parts of their procedure. Midazolam has also been shown to act synergistically with
      fentanyl, thereby decreasing not only the actual pain recalled, but the actual pain
      experienced by patients. Since the only randomized control trial demonstrating the benefits
      of paracervical block was performed using mepiridine and diazepam, we intend to repeat the
      study using the superior combination of fentanyl and midazolam.

      Study Rationale:

      The oocyte retrieval may be the most painful part of fertility treatment. Our goal is to
      minimize patient discomfort and improve overall patient experience during fertility
      treatments. We do not know if PCB improves pain scores in the era of wider use of fentanyl
      and midazolam for sedation. Fertility centres may be subjecting their patients to a painful
      PCB injection without proven benefit. This study aims to assess whether a PCB in addition to
      conscious sedation can be abandoned without impacting the patient's overall pain experience.

      Study Objective:

      The objective is to compare whether conscious sedation alone is as effective as paracervical
      block plus conscious sedation in controlling pain during oocyte retrieval

      Study Question:

      Is conscious sedation alone as effective as paracervical block plus conscious sedation in
      controlling pain during oocyte retrieval?

      Overview of the Trial Design This study is designed to be a placebo-controlled, randomised,
      double blind trial to compare whether conscious sedation with a normal saline paracervical
      block (placebo) is as effective as conscious sedation with a lidocaine paracervical block in
      controlling pain during oocyte retrieval. A total of 300 women will randomly be assigned in a
      1:1 ratio, after consenting to study participation. Short-Form McGill Pain scores will be
      assessed in study subjects.

      Study Population:

      Women presenting for oocyte retrieval after a cycle of IVF stimulation at the University of
      Alberta Regional Fertility Centre

      Study Design:

      Women consenting to participate in the study will be randomly allocated to one of two groups.
      The control group will receive conscious sedation with a placebo (normal saline) paracervical
      block (PCB). The study group will receive conscious sedation with a local anaesthetic
      (lidocaine 1%) PCB. Computer generated randomisation will be used to determine group
      allocation. Group allocation will be concealed using opaque envelopes to ensure blinding. An
      OR nurse will prepare the PCB syringe with either lidocaine or normal saline depending on the
      patient's allocation. The contents of the PCB will remain blinded from the physician
      performing the TUGOR and the patient.

      The fertility centre's routine for TUGOR is as follows: Initially conscious sedation is
      administered by OR nursing staff according to the patient's weight (midazolam 1 - 2 mg and
      fentanyl 50 - 75 ug IV). This is followed by the PCB 5 minutes later. Additional fentanyl is
      administered throughout the procedure as required to ensure patient comfort. The oocyte
      retrieval proceeds once the PCB is completed. Following the oocyte retrieval and when the
      conscious sedation has worn off; the patient will be assessed before discharge. Once the
      discharge criteria have been met, the validated and standardized Short-Form McGill Pain
      Questionnaire will be used to objectively measure the pain experienced during the TUGOR. All
      study participants will be required to rate the pain experience during the procedure. The
      attending nurse is required to record all adverse events from the procedure as part of her
      clinical duties. Embryology information, i.e. fertilization, embryo grading, development and
      frozen rates will be recorded to assess whether PCB affects this aspect of ART. Additional
      information will be obtained by reviewing participants' clinic charts nine months
      post-procedure to determine secondary outcomes, i.e. live birth rates. Animal mouse models in
      the past have shown local anaesthetic to adversely affect fertilization and embryo
      development (Schnell, 1992). No adverse effects on human embryos from lidocaine have ever
      been demonstrated (Wikland 1990), however assessing embryo quality and birth outcomes has
      been the standard when conducting studies assessing the use of PCB

      Setting:

      Academic referral fertility centre
    

Intervention name(s): Lidocaine hydrochloride (HCl) 1% solution; Sterile Normal Saline%
Intervention type(s): Drug; Drug
Intervention description(s): Comparison of paracervical block using Lidocaine versus Normal Saline placebo in patients undergoing oocyte retrieval during IVF.; Sterile normal saline used as placebo for lidocaine hydrochloride (HCl)1% solution
Other intervention name(s): Xylocaine; Sterile Normal Saline
Intervention MeSH terms: Lidocaine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Infertility