1 Department of Obstetrics and Gynaecology, The University of Western Ontario, London, Ontario, Canada 3 Department of Obstetrics and Gynaecology, Department of Psychology, The University of Western Ontario, London, Ontario, Canada
2 Present address, Mayo Clinic, 200 First Street SW, Rochester MN 55905, USA
4 Present address, Humber River Regional Hospital, Toronto, Ontario, Canada
5 Present address, Southern Ontario Fertility Technologies, London, Ontario, Canada
6 To whom correspondence should be addressed. e-mail: tummon.ian{at}mayo.edu.
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Abstract |
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Key words: analgesia/lidocaine/oocyte retrieval/pain/sedation
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Introduction |
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Barriers to use of adjunctive paracervical block are the invasive nature of administration of the block (compared with administration of lidocaine vaginal gel) and potential toxicity of absorbed lidocaine. An alternative form of adjunctive therapy is lidocaine vaginal gel, a minimally invasive administration with potential for lower reproductive toxicity.
In a preliminary randomized trial, there was a trend to lower follicular fluid lidocaine concentration with lidocaine as vaginal gel compared with paracervical block (Weeraklet et al., 1999). During paracervical block, some follicles may be exposed to high levels of lidocaine, possibly due to passage of the aspiration needle through lidocaine-infiltrated tissue. Follicular fluid lidocaine concentrations were as high as 118 µg/ml after paracervical block with 100 mg of lidocaine (Bailey-Pridham et al., 1990
). Follicular fluid lidocaine concentrations as low as 1.0 µg/ml were associated with toxic effects on fertilization and embryo development in the murine model (Schnell et al., 1992
). In human use, however, there is no evidence of adverse events associated with lidocaine paracervical block. Mean follicular fluid lidocaine concentration was 0.36 µg/ml after paracervical block with 50 mg of lidocaine (Wikland et al., 1990
). Comparison of cohorts with and without paracervical block showed no adverse effects on fertilization, cleavage or pregnancy rates (Wikland et al., 1990
).
Randomized trials of lidocaine gel in contexts other than assisted reproduction have produced results more generally non-beneficial than beneficial. In gynaecological trials, application of intrauterine lidocaine gel showed no difference from placebo when used during endometrial aspiration (Kozman et al., 2001). In contrast, perineal application of 2% lidocaine gel was associated with a modest decrease in post-partum pain (Collins et al., 1994
). In urological trials, intra-urethral or transrectal administration of lidocaine gel failed to show therapeutic benefit (Chang et al., 2001
; McFarlane et al., 2001
).
The purpose of the present trial was to compare the analgesic efficacy of two forms of adjunctive treatment to sedation for oocyte retrieval: lidocaine vaginal gel versus lidocaine paracervical block.
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Materials and methods |
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Sample size estimation was based on evidence from a previous randomized trial of lidocaine paracervical block (Corson et al., 1994) in which the authors used a pain score scale from 0 to 4. A pain score difference of 0.5 on the scale from 0 to 4 was considered relevant. Standard assumptions were
= 0.05 and power = 0.8. A sample of 65 in each group was calculated to be needed for the present trial (Cohen, 1988
).
Visual analogue scales for pain intensity are usually measured with a range from 0 to 10 and this range was chosen for the trial (Von Korff et al., 2000).
During the study interval, there were 331 patients who had oocyte retrieval. Superovulation patients converted to IVF (Nisker et al., 1994) (n = 91), as well as those who were allergic to lidocaine, were excluded. Patients undergoing primary treatment with IVF were asked to consider participation in the trial (n = 240) before starting treatment. A total of 150 participants gave consent (Figure 1)
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Masking
There was no masking. Participants were aware of their treatment assignment. The treating physician, who delivered the intervention with either vaginal gel or paracervical block, was also aware of treatment assignment.
Self-assessment of pain
Although other trials have employed physician assessment of pain, it was elected to confine outcomes to self-assessment. Patients undergoing fertility treatment may be highly motivated and reluctant to show their emotions. In an observational study, mean pain scores were lower with a physician observer assessment compared with self-assessment (Gohar et al., 1993).
Ratings of anxiety and pain before oocyte retrieval
Before oocyte retrieval, participants completed ratings indicating: current anxiety, degree of worry about oocyte retrieval and level of pain anticipated, on visual analogue scales that ranged from 0 to 10. For anxiety and worry, scale end-points ranged from 0 not at all worried to 10 extremely worried. For anticipated pain, end-points ranged from 0 no pain to 10 pain as bad as it could be.
Ratings of anxiety and pain after oocyte retrieval
After oocyte retrieval, participants rated pain during administration of lidocaine, pain during needle puncture of the vaginal wall, pain during oocyte aspiration and anxiety generally during oocyte retrieval.
Subjects were also asked to characterize the entire experience of oocyte retrieval by completing the McGill Pain Questionnaire, a standardized self-reported measure of subjective pain experience (Melzack, 1975). The questionnaire measures different aspects of the pain experience. Subjects chose words describing sensory and affective qualities of pain as well as evaluative words describing overall pain intensity. A pain rating index is calculated based on the rank value of words chosen from each category (Melzack, 1975
). The pain rating index and total number of words chosen provide two measures of total pain experience. Ranks of each chosen word are added in each category and total score of all chosen words ranked. Total pain score is calculated by adding together ranks for all words chosen on the questionnaire. There is a supplementary category of words with four groupings that patients can choose from with words such as penetrating or piercing. Total pain score, therefore, may be greater than the sum of sensory, affective and evaluative scores if supplementary words are chosen.
Ovarian stimulation
A long luteal protocol for ovarian stimulation was used as previously described (Tummon et al., 1995). Gonadotrophin dosage was chosen individually, taking into account age, body mass index (BMI), basal FSH and previous response. Ovarian response was monitored with serum estradiol and transvaginal ultrasound. Ovulation was triggered using 10 000 IU of HCG. Transvaginal oocyte retrieval was done under ultrasound guidance with a single lumen aspiration needle (Swemed Lab, distributed by Scan-Med, Middle Grove, NY).
Lidocaine vaginal gel
For participants randomized to gel, lidocaine 80 mg was used (4 ml of 2% lidocaine gel, AstraZeneca Canada Inc., Mississauga, Ontario, Canada) inserted into the posterior vaginal fornix using an applicator 30 min before oocyte retrieval.
Paracervical lidocaine block
For participants randomized to paracervical block, lidocaine 75 mg was used (15 ml of 2% lidocaine, AstraZeneca Canada Inc., Mississauga, Ontario, Canada) injected at the 4 and 8 oclock positions using a 21 gauge spinal needle, just before oocyte retrieval.
Sedative anaesthesia
All participants received i.v. fentanyl (Janssen-Ortho, Don Mills, Ontario, Canada) according to body weight. Subjects weighing 5060 kg received 50 µg of fentanyl, participants weighing from 60 to 70 kg received 75 µg of fentanyl, while participants weighing >70 kg received 100 µg of fentanyl. No additional sedation was given to either intervention group.
Data analysis
Data were managed and analysed with Medcalc 7.2.0.2 (Mariakerke, Belgium). Means were compared using independent t-tests (Klugh, 1974). Analysis was by intention-to-treat. Multiple regression was used to examine whether independent variables of age, BMI, cycle, number of punctures, number of oocytes, physician operator or intervention group were related to total pain.
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Results |
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Adverse events
No important adverse events were observed in either intervention group.
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Discussion |
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Subjects using lidocaine vaginal gel reported less pain with application of lidocaine and greater pain during insertion of the aspiration needle and follicular aspiration. Sensory and affective pain qualities were similar between intervention groups, but evaluative qualities of pain were greater with vaginal lidocaine gel compared with paracervical lidocaine block.
Participants using lidocaine vaginal gel also reported overall higher pain intensity and greater total pain experience. Apparently, the lesser degree of pain experienced during application of vaginal lidocaine gel did not compensate for the greater pain experienced during insertion of the aspiration needle and follicle aspiration.
A novel finding from the present trial was differentiation of pain between intervention groups at specific steps during oocyte retrieval. Outcome measures in previous trials did not differentiate between vaginal pain from administration of the paracervical block and insertion of the aspiration needle through the vaginal wall (Corson et al., 1994; Ng et al., 1999
). On a note of caution, in the present trial, participants were asked to differentiate pain in a retrospective fashion. While the extent to which this distinction could be made reliably is unknown, there is no clear reason why recall should favour one treatment condition over another.
Factors other than adjunctive therapies also influenced the total pain experience in the present trial. Factors positively associated with increased total pain experience were younger age, higher BMI and a greater number of treatment cycles.
Generalizability
The external validity of the present trial is derived from wide general use of the techniques used. Sedation is the most common form of anaesthesia for oocyte retrieval in both the USA and the UK (Ditkoff et al., 1997; Bokhari and Pollard, 1999
). In the UK, paracervical block is the most common regional technique used as adjunctive therapy to sedation (Bokhari and Pollard, 1999
).
General interpretation
In the present trial, total pain experienced was greater with lidocaine vaginal gel compared with lidocaine paracervical block.
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Acknowledgements |
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References |
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Submitted on October 30, 2003; accepted on February 18, 2004.
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