Abstract

BACKGROUND: The aim of this study was to compare the pain-relieving effect and the subjective well-being between auricular electro-acupuncture (EA) analgesia, auricular acupuncture (A) and conventional analgesia with remifentanil (CO). METHODS: A total of 94 women undergoing IVF were randomized to auricular acupuncture with (EA, n = 32) or without (A, n = 32) continuous 1 Hz auricular stimulation (using a battery-powered miniaturized stimulator, P-Stim) or with adhesive tapes instead of needles and no electrical stimulation (control group, CO, n = 30) at the auricular acupuncture points 29, 55 and 57. All patients received patient-controlled analgesia (PCA) with remifentanil. Pain intensity and psychological well-being were assessed by means of visual analogue scales (VAS); tiredness, nausea and vomiting and analgesic drug consumption were documented. RESULTS: Pain relief and subjective well-being were significantly greater in group EA during and after the procedure as compared with groups A and CO (P < 0.001). The patients were significantly more tired in group CO than in groups A and EA (P < 0.001). Consumption of the opioid remifentanil was significantly lower in group EA, comparable nausea (P < 0.001). CONCLUSION: Auricular EA significantly reduces pain intensity and analgesic consumption of the opioid remifentanil during oocyte aspiration in IVF treatment.

Introduction

Transvaginal ultrasound-guided oocyte aspiration has simplified the process of IVF and embryo transfer. The oocyte aspiration procedure is usually short, lasting 10–15 min, and is generally the most painful component of the IVF treatment. Pain perceived during oocyte aspiration varies to a large extent from one individual to another and is often likened to the pain perceived during menstruation (Soussis et al., 1995). The ideal analgesic treatment during oocyte retrieval should guarantee rapid onset, adequate pain relief and rapid recovery without affecting the oocytes. The use of i.v. sedation and analgesia using benzodiazepines, propofol and opioids is a common clinical practice (Soussis et al., 1995; Ditkoff et al., 1997; Trout et al., 1998; Wilhelm et al., 2002). The use of opioids and benzodiazepines, however, may frequently be associated with adverse effects such as tiredness, nausea and confusion (Volikas and Male, 2001; Wilhelm et al., 2002). Furthermore, many of these agents have been detected in the follicular fluid, albeit clear evidence to indicate negative effects on oocytes, oocyte differentiation, implantation or pregnancy rate is sparse (Stener-Victorin et al., 1999; Wilhelm et al., 2002; Stener-Victorin 2005). The standard sedoanalgesia during oocyte aspiration at our clinic consists of metamizol 1 g i.v. (Novalgin®, Aventis Pharma Germany, Frankfurt, Germany) and midazolam 2 mg per os (Dormicum®, Hoffmann-La Roche, Basel/Switzerland/F. AG/CH) with supplemental tramundal 100 mg i.v. (Tramal®, Gruenenthal, GMBH, Stolberg, Germany) if required.

Remifentanil (Ultiva®, Glaxo Wellcome Operations, Greenford, UK) is an ultra-short acting µ-agonist opioid with a rapid clearance. Recently, remifentanil has been shown to be beneficial and potentially superior to pethidine in the achievement of patient-controlled analgesia (PCA) during labour (Glass et al., 1999; Volikas and Male, 2001).

The underlying mechanism of action of auricular electro-acupuncture (EA) is suggested to be multi-factorial involving biological responses such as the stimulation of A-delta fibers by the stimulating ‘De qi’ sensation, as well as psychological aspects (Willer et al., 1984; Amanzio and Benedetti, 1999). Other potential mechanisms include the activation of descending inhibitory pain control systems (Sandkühler, 1996, 1997), activation of the propriospinal heterosegmental antinociceptive system leading to down-regulation of pain-induced changes in signal transduction in the spinal cord (Han et al., 1991; Mayer, 2000) and the release of endogenous opioid peptides (Tang et al., 1997). EA has been found to induce the release of various neurotransmitters such as encephalin and dynorphins (Ghoname et al., 1999) and substance P (White et al., 2000) in the central nervous system both in animal studies and in humans (Csemiczky and Collins, 2000). Despite both experimental and clinical evidence of the effects claimed for EA, its role in western medicine has been questioned (Renckens, 2002; Sator-Katzenschlager et al., 2003, 2004). The effect of EA as a pain-relieving method during surgical procedures has been evaluated in various situations (Stener-Victorin et al., 1999, 2003).

Most of the patients ask for non-pharmacological analgesic methods because of the negative side effects of opioids. Acupuncture, especially auricular EA, may be an alternative for patients with intolerance of conventional analgesia. To date, no study has examined the potential benefits of continuous electrical auricular acupuncture during oocyte aspiration in IVF treatment. The aim of this study was to determine the efficacy of auricular EA as a supplement to an i.v. remifentanil bolus via PCA for the short-lasting, but painful, transvaginal puncture for oocyte retrieval. The aim of this study was to test the hypothesis that auricular EA would reduce acute pain, and analgesic consumption (the use of remifentanil), and improve perioperative well-being.

Materials and methods

Study design and patient selection criteria

The study was performed at the IVF unit, Medical University of Vienna, Austria, between April and December 2004. The study protocol was designed to follow the CONSORT guidelines [randomized controlled trial (RCT)] (Moher et al., 2001). After obtaining approval from the institutional Ethics Committee at the University of Vienna and written informed consent, 94 healthy, adult female patients undergoing oocyte aspiration for IVF treatment were investigated in a prospective, randomized, double-blind, controlled study. Women undergoing a super-ovulation protocol for oocyte retrieval aged <43 years, with a BMI <28 kg/m2, who had four or more follicles >18 mm at the time of HCG injection for oocyte maturization, were selected for enrolment. Exclusion criteria were auricular acupuncture in the past, allergy to remifentanil and other opioids, history of drug abuse or chronic pain therapy, presence of a pacemaker, asthma, diabetes, corticosteroid use, eczema of the ear or history of any previous surgery of the ear. For transvaginal ultrasound-guided oocyte retrieval, all patients received metamizol 1 g i.v. (Novalgin®, Aventis Pharma, Frankfurt, Germany) infused 15 min before the procedure and a PCA (Graseby-perfusor 3300, B. Braun, Melsungen, Germany) pump containing remifentanil with a bolus option (20 µg bolus over 30 s, lockout period 1 min). The PCA treatment began before the start of the oocyte retrieval and finished upon completion of oocyte aspiration.

Enrolment and randomization

Only patients who had never had auricular acupuncture before were included in the study.

Randomization was performed by one doctor on the day of the last ultrasound examination before oocyte retrieval. Patients were randomized in proportions of 1:1:1 to treatment with EA group (n = 32), the auricular acupuncture (A) group without electrical stimulation (n = 32) or the control (CO) group without needles and electrical stimulation (n = 30). A computer-generated randomization list was used for allocation. The randomization was continued until at least 30 patients had been allocated to each group.

Each P-Stim™ was programmed by an independent technician for electrical stimulation or no stimulation before the study. To ensure blinding of the investigator, each P-Stim™ was packed in a non-transparent case, in which the respective permanent needles or adhesive tapes were also included. The packages were numbered consecutively, according to the randomization list. Patients and investigators were blinded to the randomization.

Auricular EA

An electrical conductance device meter (multipoint selection pen™, Biegler GmbH, Mauerbach, Austria) that measures the skin resistance and signals the active point with light and noise was used to identify the acupuncture points (Oleson et al., 1980). Patients of groups EA and A received auricular acupuncture using special titanium disposable needles (27 gauge, 3 mm length; Biegler GmbH). Disposable acupuncture needles were inserted in the auricular acupuncture points 57 (uterus, a specific auricular acupuncture point for pathologies concerning the uterus and adnexa), 55 (shen men, an auricular acupuncture point with strong analgesic properties) and 29 (cushion, an auricular acupuncture point with strong analgesic and psychological properties) of the dominant side. Needles were covered by adhesive tape and connected to a battery-powered miniaturized stimulator worn behind the ear (P-Stim™, Biegler GmbH) (Figure 1). We choose shen men and cushion as analgesic points and uterus, because most of the patients have uterine contractions during and after the procedure. The P-Stim™ devices were applied 30 min before the oocyte retrieval by only the same gynaecologist trained in auricular acupuncture (diploma of acupuncture, Austrian Medical Chamber with 3 years of clinical experience in acupuncture). A second gynaecologist performed the oocyte retrieval and another doctor asked the outcome parameters to ensure blinding.

Figure 1.

P-Stim™ and auricular acupuncture points. The P-Stim™ was connected to permanent auricular acupuncture needles [auricular electro-acupuncture (EA) and auricular acupuncture group] or to adhesive tapes (control group without needles and stimulation) at the auricular acupoints 57 (uterus), 55 (shen men) and 29 (cushion) and fixed behind the ear.

Figure 1.

P-Stim™ and auricular acupuncture points. The P-Stim™ was connected to permanent auricular acupuncture needles [auricular electro-acupuncture (EA) and auricular acupuncture group] or to adhesive tapes (control group without needles and stimulation) at the auricular acupoints 57 (uterus), 55 (shen men) and 29 (cushion) and fixed behind the ear.

In group EA, continuous low-frequency auricular EA with a constant current of 1 Hz biphasic, 2 mA was applied half an hour before the procedure and lasted until 1 h after the procedure. After 3 h of stimulation, a break of 3 h was programmed to minimize the potential of any adaptation or tolerance to the analgesic effects. The investigator removed the P-Stim™ devices from all patients 1 h after the end of surgery.

In groups A and CO, P-Stim™ devices were attached without electrical stimulation. Patients of group CO received only an adhesive tape over the whole ear connected to the P-Stim™. In this group, underneath the adhesive tape placed at the three auricular acupuncture points, no needles were attached.

Outcome parameters

The following outcome parameters were assessed before the application of the P-Stim™, every 3 min during the oocyte retrieval and every 10 min after the treatment until 1 h afterwards. Pain intensity and subjective well-being (Ghoname et al., 1999; Sator-Katzenschlager et al., 2003) were assessed using a visual analogue scale (VAS; 0 mm, no impairment; 100 mm, worst impairment imaginable). Nausea (0, no nausea; 1, mild nausea; 2, moderate nausea; 3, severe nausea) and tiredness (0, no tiredness; 1, mild tiredness; 2, moderate tiredness; 3, severe tiredness) were also assessed using a visual rating scale. Analgesic drug requirements during the entire study period (requested bolus and maintained bolus) were recorded. The patients’ overall satisfaction with the pain treatment was determined at the end of the study period. The questionnaire also included questions concerning blinding success and the patient’s evaluation of auricular EA, i.e. side effects, efficacy of acupuncture in relieving post-operative pain and willingness to use a P-Stim™ again. Demographic data and side effects were documented. Clinical parameters included the number of previous IVF cycles, number of retrieved oocytes, number of embryos transferred per embryo transfer, number of positive pregnancy tests and the number of pregnancy rate. An HCG-positive pregnancy test was defined by a plasma β-HCG concentration of >4 mU/ml 14 days after embryo transfer. The pregnancy rate was defined as an intrauterine gestational sac with a heartbeat, 3 weeks after a positive HCG test.

Statistical analysis

The power analysis based on a pilot study revealed that a minimum study size of 30 individuals in each group would provide 80% power (0.05α, two-tailed, 0.20β, two-tailed) of detecting a difference in mean pain intensity during surgery of VAS 2 or greater (SD = 1.1) between groups EA and A.

According to the intention-to-treat principle, data from all randomized patients were used for statistical analysis. Continuous and categorical variables were described by mean ± standard deviation (except where indicated) and frequencies (percentages), respectively. For each patient, mean values of VAS scores were calculated from all assessments during the study period. For the variables, pain intensity and well-being, overall mean VAS values and VAS assessments after the study period were approximately normally distributed as confirmed by a non-significant Shapiro-Wilk test for normality and compared between groups using analysis of covariance and Tukey’s post-hoc tests, adjusting for baseline values. The variables requested remifentanil rescue medication, received remifentanil rescue medication, tiredness, nausea and vomiting were not normally distributed and compared using non-parametric Bonferroni-corrected Mann–Whitney U-tests. Frequencies of categorical variables (pain qualities, socio-economic status) after study period were compared between groups using the chi-squared test or the Fisher’s exact test if any expected cell frequency was lower than five. P-values <0.05 were considered as statistically significant. The SAS System Version 8.2 (2001 SAS Institute, Cary, NC, USA) was used for statistical analysis.

Results

Patients and demographic data

Ninety-four female patients scheduled for oocyte aspiration during IVF-treatment were enrolled in the study. One patient of group CO was not eligible for further analysis due to impaired compliance while wearing the P-Stim™ device. This patient refused to further participate in the study, and so no follow-up data were available from this patient (Figure 2).

Figure 2.

Flow diagram through different stages of the randomized controlled trial (RCT). Withdrawal: number of patients who refused to further participate in the study and in whom no data are available. Follow up: number of patients who continued the study. A, auricular acupuncture; CO, control group (without needles and stimulation); EA, auricular electro-acupuncture.

Figure 2.

Flow diagram through different stages of the randomized controlled trial (RCT). Withdrawal: number of patients who refused to further participate in the study and in whom no data are available. Follow up: number of patients who continued the study. A, auricular acupuncture; CO, control group (without needles and stimulation); EA, auricular electro-acupuncture.

Accordingly, 93 patients were analysed. There were no relevant differences in age, weight and height between groups EA, A and CO, respectively (Table I).

Table I.

Demographics and outcome variables of IVF treatment in the group receiving electro-acupuncture with remifentanil (EA) and acupuncture with remifentanil (A) and the group receiving remifentanil and placebo (CO)

Demographics EA (n = 32) A (n = 32) CO (n = 30) 
Age (years) 33.3 ± 1.7 34.2 ± 1.1 33.9 ± 1.9 
Weight (kg) 65.2 ± 10.6 64.2 ± 12.5 64.9 ± 12.3 
Height (cm) 166.3 ± 6.1 164.9 ± 7.7 164.0 ± 8.1 
Cause of infertility [n (%)] 
    Male factor 12 (37.5) 13 (40.6) 11 (36.7) 
    Tubal disease 4 (12.5) 6 (18.8) 4 (13.3) 
    Endometriosis 5 (15.6) 6 (18.8) 6 (20.0) 
    PCOS 2 (6.3) 1 (3.1) 0 (0) 
    Two causes 2 (6.3) 0 (0) 0 (0) 
    Other causes 1 (3.2) 0 (0) 1 (3.3) 
    Unexplained 6 (18.8) 7 (28.1) 8 (30.0) 
Total 32 (100) 32 (100) 30 (100) 
Number of IVF treatments 
    Zero attempt 5 (15.6) 6 (19.4) 9 (30.0) 
    One attempt 12 (37.5) 9 (29.0) 11 (36.7) 
    Two attempts 9 (28.1) 9 (29.0) 6 (20.0) 
    Three attempts 3 (9.4) 2 (6.5) 3 (10.0) 
    Four attempts 1 (3.1) 3 (9.7) 1 (3.3) 
    Five attempts 0 (0) 1 (3.2) 0 (0) 
    Six attempts 1 (3.1) 1 (3.2) 0 (0) 
    Seven attempts 1 (3.1) 0 (0) 0 (0) 
Number of follicles 13.4 ± 7.4 12.2 ± 8.8 13.6 ± 7.1 
Number of oocytes retrieved 9.9 ± 5.2 8.7 ± 4.8 9.1 ± 5.1 
Time for oocyte retrieval (minutes) 9.8 ± 4.2 8.9 ± 5.3 9.6 ± 5.2 
Oocyte aspirations 32 32 30 
Embryo transfers 32 32 27 
Pregnancy rate per transfer 19 (59.4%) 11 (34.4%) 7 (24.1%) 
Demographics EA (n = 32) A (n = 32) CO (n = 30) 
Age (years) 33.3 ± 1.7 34.2 ± 1.1 33.9 ± 1.9 
Weight (kg) 65.2 ± 10.6 64.2 ± 12.5 64.9 ± 12.3 
Height (cm) 166.3 ± 6.1 164.9 ± 7.7 164.0 ± 8.1 
Cause of infertility [n (%)] 
    Male factor 12 (37.5) 13 (40.6) 11 (36.7) 
    Tubal disease 4 (12.5) 6 (18.8) 4 (13.3) 
    Endometriosis 5 (15.6) 6 (18.8) 6 (20.0) 
    PCOS 2 (6.3) 1 (3.1) 0 (0) 
    Two causes 2 (6.3) 0 (0) 0 (0) 
    Other causes 1 (3.2) 0 (0) 1 (3.3) 
    Unexplained 6 (18.8) 7 (28.1) 8 (30.0) 
Total 32 (100) 32 (100) 30 (100) 
Number of IVF treatments 
    Zero attempt 5 (15.6) 6 (19.4) 9 (30.0) 
    One attempt 12 (37.5) 9 (29.0) 11 (36.7) 
    Two attempts 9 (28.1) 9 (29.0) 6 (20.0) 
    Three attempts 3 (9.4) 2 (6.5) 3 (10.0) 
    Four attempts 1 (3.1) 3 (9.7) 1 (3.3) 
    Five attempts 0 (0) 1 (3.2) 0 (0) 
    Six attempts 1 (3.1) 1 (3.2) 0 (0) 
    Seven attempts 1 (3.1) 0 (0) 0 (0) 
Number of follicles 13.4 ± 7.4 12.2 ± 8.8 13.6 ± 7.1 
Number of oocytes retrieved 9.9 ± 5.2 8.7 ± 4.8 9.1 ± 5.1 
Time for oocyte retrieval (minutes) 9.8 ± 4.2 8.9 ± 5.3 9.6 ± 5.2 
Oocyte aspirations 32 32 30 
Embryo transfers 32 32 27 
Pregnancy rate per transfer 19 (59.4%) 11 (34.4%) 7 (24.1%) 

PCOS, polycystic ovary syndrome.

Data are mean ± SD (percentage).

Pain intensity

Pain intensity increased from baseline in all groups during oocyte aspiration (Figure 3A). Mean (and maximum) pain intensity during surgery, however, was significantly lower in group EA (mean VAS 2.9 ± 1.5; max VAS 6.7) compared with group A (mean VAS 4.9 ± 1.7; max VAS 8.7) and group CO (mean VAS 5.9 ± 1.6; max VAS 10.0). After the procedure, pain intensity remained significantly lower in group EA (VAS 1.1 ± 1.4) compared with group A (VAS 2.6 ± 1.4) and group CO (VAS 3.2 ± 1.4). All patients in group EA experienced pain reduction; no case of non-responding was recorded. Consumption of remifentanil rescue medication was significantly higher in the group CO when compared with groups A and EA (median, minimum–maximum requested bolus: 10, 6–27 versus 6, 2–21 versus 2, 0–5, and received bolus: 8, 4–13 versus 5, 2–8 versus 2, 0–4 during the entire investigation period).

Figure 3.

Effect of auricular electro-acupuncture (group EA), acupuncture (group A) or placebo (group CO) on pain intensity (A), subjective well-being (B) in patients during oocyte aspiration in IVF treatment. Data are presented as means ± SD. Pain intensity and subjective well-being were assessed by visual analogue scale (VAS) ranging from 0 mm = no impairment to 100 mm = worst deterioration imaginable. The degree of tiredness and degree of nausea were assessed by using a verbal rating scale (0, no; 1, mild; 2, moderate; 3, severe), *P < 0.005 versus group EA. #P < 0.005 versus group A.

Figure 3.

Effect of auricular electro-acupuncture (group EA), acupuncture (group A) or placebo (group CO) on pain intensity (A), subjective well-being (B) in patients during oocyte aspiration in IVF treatment. Data are presented as means ± SD. Pain intensity and subjective well-being were assessed by visual analogue scale (VAS) ranging from 0 mm = no impairment to 100 mm = worst deterioration imaginable. The degree of tiredness and degree of nausea were assessed by using a verbal rating scale (0, no; 1, mild; 2, moderate; 3, severe), *P < 0.005 versus group EA. #P < 0.005 versus group A.

Subjective well-being

All three groups showed deterioration in overall well-being during oocyte aspiration (Figure 3B). However, well-being scores during surgery were significantly better in group EA (VAS 3.3 ± 1.4) compared with group A (VAS 4.5 ± 1.4) and group CO (VAS 4.98 ± 1.4). After the procedure, well-being scores remained significantly better (less impairment) in group EA compared with groups A and CO.

Tiredness and nausea

During and after oocyte aspiration, tiredness was significantly more pronounced in group CO than in groups A and EA (Table II).

Table II.

Tiredness and nausea

 EA (n = 32) A (n = 32) CO (n = 30) 
Tiredness    
    Before treatment 0 (0–2)     0 (0–1) 0 (0–1) 
    During treatment 0 (0–3) 1.4 (0–3) 2 (0–3) 
    1 h post-treatment 0 (0–1) 0 (0–2) 1 (0–2) 
Nausea    
    Before treatment 0 (0–1) 0 (0–0) 0 (0–0) 
    During treatment 0 (0–1) 0 (0–1) 0 (0–1) 
    1 h post-treatment 0 (0–0) 0 (0–0) 0 (0–2) 
Vomiting    
    Before treatment 0 (0–0) 0 (0–0) 0 (0–0) 
    During treatment 0 (0–0) 0 (0–0) 0 (0–0) 
    1 h post-treatment 0 (0–0) 0 (0–0) 0 (0–2) 
 EA (n = 32) A (n = 32) CO (n = 30) 
Tiredness    
    Before treatment 0 (0–2)     0 (0–1) 0 (0–1) 
    During treatment 0 (0–3) 1.4 (0–3) 2 (0–3) 
    1 h post-treatment 0 (0–1) 0 (0–2) 1 (0–2) 
Nausea    
    Before treatment 0 (0–1) 0 (0–0) 0 (0–0) 
    During treatment 0 (0–1) 0 (0–1) 0 (0–1) 
    1 h post-treatment 0 (0–0) 0 (0–0) 0 (0–2) 
Vomiting    
    Before treatment 0 (0–0) 0 (0–0) 0 (0–0) 
    During treatment 0 (0–0) 0 (0–0) 0 (0–0) 
    1 h post-treatment 0 (0–0) 0 (0–0) 0 (0–2) 

Data are given as median (minimum and maximum)

Seven patients in group EA (21.9%), five patients in group A (15.6%) and seven patients in group CO (24.1%) reported nausea during the procedure without inter-group statistical significance (P = 0.6904; Table II). After surgery, only two patients of group CO (6.9%) reported nausea and vomiting (Table II).

Side effects of acupuncture and patient satisfaction

No adverse side effects of acupuncture per se such as needle-induced hypotension, haematoma or local auricular infection were observed. Ninety-two percent of patients in group EA, 94% in group A and 96% in group CO rated the comfort of wearing the P-Stim™ device as good; 9% in group EA, 6% in group A and 4% in group CO classified the comfort of wearing the device as moderate. Only patients of group CO rejected to use an auricular acupuncture device again because of inadequate comfort (75%) or limited analgesic effects (34.5%). All patients in groups EA and A were satisfied and would repeat pain treatment if necessary.

IVF outcome data

The indications for IVF were male factor infertility, tubal disease, endometriosis, polycystic ovary syndrome as well as unexplained infertility and were equally distributed among the three groups (Table I). The causes of infertility and the number of IVF treatments did not differ between the three groups (Table I). There were no differences between the listed indications for IVF and subsequent pregnancy success. No significant difference was found between the groups EA, A and CO in the mean number of follicles and oocytes retrieved. There were no differences between the mean time (minutes) for oocyte retrieval in the three groups (Table I). The time for mobilization and the total time at the clinic were similar between groups. Two embryos (3 and 4 score) (Steer et al., 1992) were transferred in all patients of the three groups. The transfer of the embryos in all three groups was equal, either on the third or fifth day. In the EA and A groups, 32 women underwent oocyte aspirations and 32 embryo transfers; in the CO group, 30 underwent oocyte aspirations and 27 embryo transfers. The reasons for not performing embryo transfer were absence of fertilization, no oocytes or spermatozoa found on the day of aspiration or embryo degeneration. Pregnancy per transfer rate was significantly higher in group EA compared with groups A and CO (Table I).

Discussion

This study demonstrates a significant pain relief from adjuvant auricular EA in patients undergoing oocyte aspiration and receiving i.v. PCA with remifentanil. This conclusion is supported not only by the patients’ subjective pain assessments (Figure 3A) but also by the opioid requirements. Auricular EA improved subjective well-being of patients during and after surgery and reduced tiredness and nausea, side effects of transvaginal oocyte aspiration and opioid analgesia (Figure 3B). Together, these results suggest major advantages of EA in the clinical management of IVF patients. Previous studies observed no negative side effects of body (not auricular) EA during oocyte aspiration (Stener-Victorin et al., 1999, 2003). According to our clinical experience, one major advantage of auricular over body EA is increased patient comfort because of the miniaturized stimulator unit and the lack of body-wrapping wires connecting the stimulator unit and the needles.

Conscious sedation is the most widely used method for the pain relief during oocyte retrieval (Trout et al., 1998). Some IVF units perform paracervical blocks which have been successful as an adjunct to conscious sedation for pain relief during oocyte retrieval (Ng et al., 1999, 2000). The authors described that the paracervical block is as a good method to reduce the levels of abdominal pain during the surgery (Ng et al., 1999, 2000). Paracervical blockades with conscious sedation have been compared with paracervical blockades with body EA, which was a good alternative to the conventional medical analgesia (Stener-Victorin et al., 2003). We are the first to evaluate auricular EA. This additive procedure is less invasive and perhaps good for women who are intolerant of conventional analgesia and prefer non-pharmacological analgesic method.

Although in the past, scepticism has been voiced regarding the effects claimed for acupuncture, in recent years, the effect of acupuncture on different conditions (pain and diseases) has been studied from a Western scientific perspective, and the results have demonstrated that acupuncture has both physiological and psychological effects (Andersson and Lundeberg, 1995). Electrical stimulation of acupuncture points is considered to increase acupuncture analgesia (Gejervall et al. 2005). The significant pain reduction under EA in patients with chronic cervical and back pain has been reported previously (Sator-Katzenschlager et al., 2003, 2004). The present data in acute pain patients extend these previous studies in chronic pain patients (Sator-Katzenschlager et al., 2003, 2004) and confirm that EA induces adequate perioperative analgesia in minor surgery, as well as a significant decrease in opioid requirements and opioid-related side effects (Kho et al., 1991; Wang et al., 1997; Stener-Victorin et al., 1999, 2003). Both low-frequency stimulation and high-frequency stimulation have been found to induce analgesia, but different types of endorphins are released depending on the stimulation pattern (Tang et al., 1997; White et al., 2000). Cumulative analgesic effects may be achieved by longer electrical stimulation periods (Ghoname et al., 1999).

Many couples undergoing IVF suffer great stress and anxiety and may need to repeat the treatment (cycle) before the achievement of pregnancy and delivery. Therefore, it is important to avoid or at least reduce the sensation of disconcerting events during the oocyte aspiration procedure. Psychological well-being may affect the implantation rate (Csemiczky and Collins, 2000). In our study, all patients received remifentanil. Even in this group of patients with higher pregnancy rate compared with general anaesthesia during transvaginal oocyte retrieval (Wilhelm et al., 2002), further improvements could be achieved by EA. Interestingly, both well-being and pregnancy rate were significantly higher in patients receiving auricular EA. Although this finding on the effect of EA on pregnancy rate is in accordance with previous observations (Andersson and Lundeberg, 1995; Stener-Victorin et al., 1999; Gejervall et al., 2005), the number of patients does not allow for generalization of our observations. A clinical study including a larger number of patients is currently in progress to further clarify this issue.

Electrical stimulation of the auricular acupuncture points permitted a fully double-blinded study protocol in this study. The stimulator was either activated or not activated by a technician who was not otherwise involved in the study. Obviously, difficulties with blinding have always been discussed as a critical point of these studies and have proven one of the major problems for adequate validation of the effectiveness of acupuncture (Kleinhenz et al., 1999). The data presented cannot refute the hypothesis that all benefits from pain treatments are because of non-specific effects of participation in the study, contact with the pain therapist or patient expectation.

Our findings may have major implications to the clinical management of assisted reproduction. The use of the P-Stim™ is easy and does not require long-lasting, sophisticated training in acupuncture and traditional Chinese medicine. P-Stim™ can be easily applied by the consultant anaesthesiologist, pain therapist or other physician who is trained in acupuncture. We observed no adverse side effects of EA per se. EA can be recommended as a safe, additive, non-pharmacological pain treatment in this clinical setting. P-Stim™ achieves our stated demands of treatment in this clinical application with a rapid onset of an adequate pain relief and rapid recovery. However, limitations are the availability of P-Stim™ only in the European community at present and the costs (50 Euro per P-Stim™ device). Furthermore, because all patients requested PCA remifentanil, EA appears to be insufficient as a sole analgesic method. Although small bolus (20 µg) and safe lockout intervals (1 min) minimize the risk of respiratory depression, the use of the i.v. opioid remifentanil PCA requires observation by a physician who is able to diagnose and manage these serious side effects.

In conclusion, EA is a good additive therapy, especially in women who are intolerant to conventional analgesia and prefer a non-pharmacological analgesic method, but cannot be recommended as the sole pain-relieving method at oocyte aspiration.

Prospective randomized controlled studies are needed to evaluate the efficacy of auricular EA in female fertility treatment.

References

Amanzio
M
Benedetti
F
Neuropharmacological dissection of placebo analgesia: expectation-activated opioid systems versus conditioning-activated specific subsystems
J Neurosci
 , 
1999
, vol. 
19
 (pg. 
484
-
494
)
Andersson
S
Lundeberg
T
Acupuncture – from empiricism to science: functional background to acupuncture effects in pain and disease
Med Hypotheses
 , 
1995
, vol. 
45
 (pg. 
271
-
281
)
Csemiczky
GLB
Collins
A
The influence of stress and state anxiety on the outcome of IVF-treatment: psychological and endocrinological assessment of Swedish women entering IVF-treatment
Acta Obstet Gynecol Scand
 , 
2000
, vol. 
79
 (pg. 
113
-
118
)
Ditkoff
EC
Plumb
J
Selick
A
Sauer
MV
Anesthesia practices in the United States common to in vitro fertilization (IVF) centers
J Assist Reprod Genet
 , 
1997
, vol. 
14
 (pg. 
145
-
147
)
Gejervall
AL
Stener-Victorin
E
Moller
A
Janson
PO
Werner
C
Bergh
C
Electro-acupuncture versus conventional analgesia: a comparison of pain levels during oocyte aspiration and patients’ experiences of well-being after surgery
Hum Reprod
 , 
2005
, vol. 
20
 (pg. 
728
-
735
)
Ghoname
ES
Craig
WF
White
PF
Ahmed
HE
Hamza
MA
Gajraj
NM
Vakharia
AS
Noe
CE
The effect of stimulus frequency on the analgesic response to percutaneous electrical nerve stimulation in patients with chronic low back pain
Anesth Analg
 , 
1999
, vol. 
88
 (pg. 
841
-
846
)
Glass
PS
Gan
TJ
Howell
S
A review of the pharmacokinetics and pharmacodynamics of remifentanil
Anesth Analg
 , 
1999
, vol. 
89
 (pg. 
7
-
14
)
Han
JS
Chen
XH
Sun
SL
Xu
XJ
Yuan
Y
Yan
SC
Hao
JX
Terenius
L
Effect of low- and high-frequency TENS on Met-enkephalin-Arg-Phe and dynorphin A immunoreactivity in human lumbar CSF
Pain
 , 
1991
, vol. 
47
 (pg. 
295
-
298
)
Kho
HG
Eijk
RJ
Kapteijns
WM
van Egmond
J
Acupuncture and transcutaneous stimulation analgesia in comparison with moderate-dose fentanyl anaesthesia in major surgery. Clinical efficacy and influence on recovery and morbidity
Anaesthesia
 , 
1991
, vol. 
46
 (pg. 
129
-
135
)
Kleinhenz
JSK
Windeler
J
Gussbacher
A
Mavridis
G
Martin
E
Randomised clinical trial comparing the effects of acupuncture and a newly designed placebo needle in rotator cuff tendinitis
Pain
 , 
1999
, vol. 
83
 (pg. 
235
-
241
)
Mayer
DJ
Biological mechanisms of acupuncture
Prog Brain Res
 , 
2000
, vol. 
122
 (pg. 
457
-
477
)
Moher
D
Schulz
KF
Altman
DG
The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials
Ann Intern Med
 , 
2001
, vol. 
134
 (pg. 
657
-
662
)
Ng
EH
Tang
OS
Chui
DK
Ho
PC
A prospective, randomized, double-blind and placebo-controlled study to assess the efficacy of paracervical block in the pain relief during egg collection in IVF
Hum Reprod
 , 
1999
, vol. 
14
 (pg. 
2783
-
2787
)
Ng
EH
Tang
OS
Chui
DK
Ho
PC
Comparison of two different doses of lignocaine used in paracervical block during oocyte collection in an IVF programme
Hum Reprod
 , 
2000
, vol. 
15
 (pg. 
2148
-
2151
)
Oleson
T
Kroening
RJ
Bresler
DE
An experimental evaluation of auricular diagnosis: the somatotopic mapping or musculoskeletal pain at ear acupuncture points
Pain
 , 
1980
, vol. 
8
 (pg. 
217
-
229
)
Renckens
CN
The sharp end of medical practice: the use of acupuncture in obstetrics and gynaecology
BJOG
 , 
2002
, vol. 
109
 (pg. 
1418
-
1419
)
Sandkühler
J
The organization and function of endogenous antinociceptive systems
Prog Neurobiol
 , 
1996
, vol. 
1
 (pg. 
49
-
81
)
Sandkühler
J
Low frequency stimulation of afferent A-delta fibers induces long-term depression of primary afferent synapses with substantia gelatinosa neurons in the rat
J Neurosci
 , 
1997
, vol. 
17
 (pg. 
483
-
491
)
Sator-Katzenschlager
SM
Szeles
JC
Scharbert
G
Michalek-Sauberer
A
Kober
A
Heinze
G
Kozek-Langenecker
SA
Electrical stimulation of auricular acupuncture points is more effective than conventional manual auricular acupuncture in chronic cervical pain: a pilot study
Anesth Analg
 , 
2003
, vol. 
97
 (pg. 
1469
-
1473
)
Sator-Katzenschlager
SM
Scharbert
G
Kozek-Langenecker
SA
Szeles
JC
Finster
G
Schiesser
AW
Heinze
G
Kress
HG
The short- and long-term benefit in chronic low back pain through adjuvant electrical versus manual auricular acupuncture
Anesth Analg
 , 
2004
, vol. 
98
 (pg. 
1359
-
1364
)
Soussis
I
Boyd
O
Paraschos
T
Duffy
S
Bower
S
Troughton
P
Lowe
J
Grounds
R
Follicular fluid levels of midazolam, fentanyl, and alfentanil during transvaginal oocyte retrieval
Fertil Steril
 , 
1995
, vol. 
64
 (pg. 
1003
-
1007
)
Steer
CV
Mills
CL
Tan
SL
Campbell
S
Edwards
RG
The cumulative embryo score: a predictive embryo scoring technique to select the optimal number of embryos to transfer in an in-vitro fertilization and embryo transfer programme
Hum Reprod
 , 
1992
, vol. 
7
 (pg. 
117
-
119
)
Stener-Victorin
E
The pain-relieving effect of electro-acupuncture and conventional medical analgesic methods during oocyte retrieval: a systematic review of randomized controlled trials
Hum Reprod
 , 
2005
, vol. 
20
 (pg. 
339
-
349
)
Stener-Victorin
E
Waldenstrom
U
Nilsson
L
Wikland
M
Janson
PO
A prospective randomized study of electro-acupuncture versus alfentanil as anaesthesia during oocyte aspiration in in-vitro fertilization
Hum Reprod
 , 
1999
, vol. 
14
 (pg. 
2480
-
2484
)
Stener-Victorin
E
Waldenstrom
U
Wikland
M
Nilsson
L
Hagglund
L
Lundeberg
T
Electro-acupuncture as a peroperative analgesic method and its effects on implantation rate and neuropeptide Y concentrations in follicular fluid
Hum Reprod
 , 
2003
, vol. 
18
 (pg. 
1454
-
1460
)
Tang
NM
Dong
HW
Wang
XM
Tsui
ZC
Han
JS
Cholecystokinin antisense RNA increases the analgesic effect induced by electroacupuncture or low dose morphine: conversion of low responder rats into high responders
Pain
 , 
1997
, vol. 
71
 (pg. 
71
-
80
)
Trout
SW
Vallerand
AH
Kemmann
E
Conscious sedation for in vitro fertilization
Fertil Steril
 , 
1998
, vol. 
69
 (pg. 
799
-
808
)
Volikas
I
Male
D
A comparison of pethidine and remifentanil patient-controlled analgesia in labour
Int J Obstet Anesth
 , 
2001
, vol. 
10
 (pg. 
86
-
90
)
Wang
HH
Chang
YH
Liu
DM
Ho
YJ
A clinical study on physiological response in electroacupuncture analgesia and meperidine analgesia for colonoscopy
Am J Chin Med
 , 
1997
, vol. 
25
 (pg. 
13
-
20
)
White
PF
Craig
WF
Vakharia
AS
Ghoname
E
Ahmed
HE
Hamza
MA
Percutaneous neuromodulation therapy: does the location of electrical stimulation effect the acute analgesic response?
Anesth Analg
 , 
2000
, vol. 
91
 (pg. 
949
-
954
)
Wilhelm
W
Hammadeh
ME
White
PF
Georg
T
Fleser
R
Biedler
A
General anesthesia versus monitored anesthesia care with remifentanil for assisted reproductive technologies: effect on pregnancy rate
J Clin Anesth
 , 
2002
, vol. 
14
 (pg. 
1
-
5
)
Willer
JC
Roby
A
Le Bars
D
Psychophysical and electrophysiological approaches to the pain-relieving effects of heterotopic nociceptive stimuli
Brain
 , 
1984
, vol. 
107
 (pg. 
1095
-
1112
)
© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. for Permissions, please email: journals.permissions@oxfordjournals.org The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org