Pain relief for women undergoing oocyte retrieval for assisted reproduction
ABSTRACT Various methods of conscious sedation and analgesia have been used for pain relief during oocyte recovery in in vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) procedures. The choice of agent has also been influenced by the quality of sedation and analgesia as well as by concerns about possible detrimental effects on reproductive outcomes.
To assess the effectiveness and safety of different methods of conscious sedation and analgesia on pain relief and pregnancy outcomes in women undergoing transvaginal oocyte retrieval.
We searched the Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL (from their inception to present); the National Research Register and Current Controlled Trials. We searched reference lists of included studies for relevant studies and contacted authors for information on unpublished and ongoing trials. There was no language restriction. The search was updated in July 2012.
Only randomised controlled trials comparing different methods of conscious sedation and analgesia for pain relief during oocyte recovery were included.
Quality assessment and data extraction were performed independently by two review authors. Interventions were classified and analysed under broad categories or strategies of sedation and pain relief to compare different methods and administrative protocols of conscious sedation and analgesia. Outcomes were extracted and the data were pooled when appropriate.
With this update, nine new studies were identified resulting in a total of 21 trials including 2974 women undergoing oocyte retrieval. These trials compared five different categories of conscious sedation and analgesia: 1) conscious sedation and analgesia versus placebo; 2) conscious sedation and analgesia versus other active interventions such as general and acupuncture anaesthesia; 3) conscious sedation and analgesia plus paracervical block versus other active interventions such as general, spinal and acupuncture anaesthesia; 4) patient-controlled conscious sedation and analgesia versus physician-administered conscious sedation and analgesia; and 5) conscious sedation and analgesia with different agents or dosage. Evidence was generally of low quality, mainly due to poor reporting of methods, small sample sizes and inconsistency between the trials.Conflicting results were shown for women's experience of pain. Compared to conscious sedation alone, more effective pain relief was reported when conscious sedation was combined with electro-acupuncture: intra-operative pain mean difference (MD) on 1 to 10 visual analogue scale (VAS) of 3.00 (95% CI 2.23 to 3.77); post-operative pain MD in VAS units of 2.10 (95% CI 1.40 to 2.80; N = 61, one trial, low quality evidence); or paracervical block (MD not calculable).The pooled data of four trials showed a significantly lower intra-operative pain score with conscious sedation plus paracervical block than with electro-acupuncture plus paracervical block (MD on 10-point VAS of -0.66; 95% CI -0.93 to -0.39; N = 781, 4 trials, low quality evidence) with significant statistical heterogeneity (I(2) = 76%). Patient-controlled sedation and analgesia was associated with more intra-operative pain than physician-administered sedation and analgesia (MD on 10-point VAS of 0.60; 95% CI 0.16 to 1.03; N = 379, 4 trials, low quality evidence) with high statistical heterogeneity (I(2) = 83%). Post-operative pain was reported in only nine studies. As different types and dosages of sedative and analgesic agents, as well as administrative protocols and assessment tools, were used in these trials the data should be interpreted with caution.There was no evidence of a significant difference in pregnancy rate in the 12 studies which assessed this outcome, and pooled data of four trials comparing electro-acupuncture combined with paracervical block with conscious sedation and analgesia plus paracervical block showed an odds ratio (OR) of 0.96 (95% CI 0.72 to 1.29; N = 783, 4 trials) for pregnancy. High levels of women's satisfaction were reported for all modalities of conscious sedation and analgesia as assessed in 12 studies. Meta-analysis of all the studies was not attempted due to considerable heterogeneity.For the rest of the trials a descriptive summary of the outcomes was presented.
The evidence from this review of 21 randomised controlled trials did not support one particular method or technique over another in providing effective conscious sedation and analgesia for pain relief during and after oocyte recovery. The simultaneous use of more than one method of sedation and pain relief resulted in better pain relief than one modality alone. The various approaches and techniques reviewed appeared to be acceptable and were associated with a high degree of satisfaction in women. As women vary in their experience of pain and in coping strategies, the optimal method may be individualised depending on the preferences of both the women and the clinicians and resource availability.
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ABSTRACT: BACKGROUND Recent systematic reviews of adjuvant acupuncture for IVF have pooled heterogeneous trials, without examining variables that might explain the heterogeneity. The aims of our meta-analysis were to quantify the overall pooled effects of adjuvant acupuncture on IVF clinical pregnancy success rates, and evaluate whether study design-, treatment- and population-related factors influence effect estimates.METHODS We included randomized controlled trials that compared needle acupuncture administered within 1 day of embryo transfer, versus sham acupuncture or no adjuvant treatment. Our primary outcome was clinical pregnancy rates. We obtained from all investigators additional methodological details and outcome data not included in their original publications. We analysed sham-controlled and no adjuvant treatment-controlled trials separately, but since there were no large or significant differences between these two subsets, we pooled all trials for subgroup analyses. We prespecified 11 subgroup variables (5 clinical and 6 methodological) to investigate sources of heterogeneity, using single covariate meta-regressions.RESULTSSixteen trials (4021 participants) were included in the meta-analyses. There was no statistically significant difference between acupuncture and controls when combining all trials [risk ratio (RR) 1.12, 95% confidence interval (CI), 0.96-1.31; I(2) = 68%; 16 trials; 4021 participants], or when restricting to sham-controlled (RR 1.02, 0.83-1.26; I(2) = 66%; 7 trials; 2044 participants) or no adjuvant treatment-controlled trials (RR 1.22, 0.97-1.52; I(2) = 67%; 9 trials; 1977 participants). The type of control used did not significantly explain the statistical heterogeneity (interaction P = 0.27). Baseline pregnancy rate, measured as the observed rate of clinical pregnancy in the control group of each trial, was a statistically significant effect modifier (interaction P < 0.001), and this covariate explained most of the heterogeneity of the effects of adjuvant acupuncture across all trials (adjusted R(2) = 93%; I(2) residual = 9%). Trials with lower control group rates of clinical pregnancy showed larger effects of adjuvant acupuncture (RR 1.53, 1.28-1.84; 7 trials; 1732 participants) than trials with higher control group rates of clinical pregnancy (RR 0.90, 0.80-1.01; 9 trials; 2289 participants). The asymmetric funnel plot showed a tendency for the intervention effects to be more beneficial in smaller trials.CONCLUSIONS We found no pooled benefit of adjuvant acupuncture for IVF. The subgroup finding of a benefit in trials with lower, but not higher, baseline pregnancy rates (the only statistically significant subgroup finding in our earlier review) has been confirmed in this update, and was not explained by any confounding variables evaluated. However, this baseline pregnancy rate subgroup finding among published trials requires further confirmation and exploration in additional studies because of the multiple subgroup tests conducted, the risk of unidentified confounders, the multiple different factors that determine baseline rates, and the possibility of publication bias.Human Reproduction Update 06/2013; 19(6). DOI:10.1093/humupd/dmt026 · 8.66 Impact Factor
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ABSTRACT: As many as one in six couples will encounter problems with fertility, defined as failure to achieve a clinical pregnancy after regular intercourse for 12 months. Increasingly, couples are turning to assisted reproductive technology (ART) for help with conceiving and ultimately giving birth to a healthy live baby of their own. Fertility treatments are complex, and each ART cycle consists of several steps. If one of the steps is incorrectly applied, the stakes are high as conception may not occur. With this in mind, it is important that each step of the ART cycle is supported by good evidence from well-designed studies. To summarise the evidence from Cochrane systematic reviews on procedures and treatment options available to couples with subfertility undergoing assisted reproductive technology (ART). Published Cochrane systematic reviews of couples undergoing ART (in vitro fertilisation or intracytoplasmic sperm injection) were eligible for inclusion in the overview. We also identified Cochrane reviews in preparation, for future inclusion.The outcomes of the overview were live birth (primary outcome), clinical pregnancy, multiple pregnancy, miscarriage and ovarian hyperstimulation syndrome (secondary outcomes). Studies of intrauterine insemination and ovulation induction were excluded.Selection of systematic reviews, data extraction and quality assessment were undertaken in duplicate. Review quality was assessed by using the AMSTAR tool. Reviews were organised by their relevance to specific stages in the ART cycle. Their findings were summarised in the text and data for each outcome were reported in 'Additional tables'. Fifty-four systematic reviews published in The Cochrane Library were included. All were high quality. Thirty reviews identified interventions that were effective (n = 18) or promising (n = 12), 13 reviews identified interventions that were either ineffective (n = 3) or possibly ineffective (n=10), and 11 reviews were unable to draw conclusions due to lack of evidence.An additional 15 protocols and two titles were identified for future inclusion in this overview. This overview provides the most up to date evidence on ART cycles from systematic reviews of randomised controlled trials. Fertility treatments are costly and the stakes are high. Using the best available evidence to optimise outcomes is best practice. The evidence from this overview could be used to develop clinical practice guidelines and protocols for use in daily clinical practice, in order to improve live birth rates and reduce rates of multiple pregnancy, cycle cancellation and ovarian hyperstimulation syndrome.Cochrane database of systematic reviews (Online) 08/2013; 8(8):CD010537. DOI:10.1002/14651858.CD010537.pub2 · 5.94 Impact Factor
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ABSTRACT: Background Pethidine with midazolam-induced conscious sedation for pain relief during transvaginal oocyte retrieval for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) procedures is associated with residual pain and oversedation. Patient-controlled analgesia (PCA) with remifentanil may serve as an alternative for pethidine. We investigated whether PCA remifentanil with diclofenac was associated with improved periprocedural pain relief than pethidine analgesia during IVF/ICSI procedures, with sedation scores, safety profiles, and patient satisfaction as secondary endpoints.Methods Seventy-six women were randomized to receive pethidine (2 mg/kg i.m.) and midazolam (7.5 mg)-induced conscious sedation (n = 40) or PCA with remifentanil and diclofenac (50 mg; n = 36). The Numeric Rating Scale, McGill Pain Questionnaire (MPQ), Ramsey Sedation Scale, and a 5-day pain-and-discomfort diary were used to evaluate pain and sedation levels.ResultsThere were no differences in baseline characteristics and reproductive outcomes between both groups. Periprocedural pain scores were comparable for remifentanil and pethidine groups (4 [3 to 7] vs. 6 [4 to 8]; P = 0.13). Pain scores in the pethidine group were significantly lower at 30 minutes after the procedure (1 [0 to 3] vs. 2 [1 to 5]; P = 0.016), but at cost of higher sedation levels when compared to remifentanil (4 [2 to 4] vs. 2 [2 to 2]; P < 0.001). Patient satisfaction was higher, and MPQ scores were lower in the remifentanil group. There were no differences in safety profiles between both analgesics.Conclusions Patient-controlled analgesia with remifentanil showed a similar reduction in pain scores than pethidine with midazolam during oocyte retrieval, while pethidine induced the highest pain relief after the procedure. However, PCA remifentanil was associated with less sedation and a better patient satisfaction profile than pethidine.Pain Practice 04/2014; 15(5). DOI:10.1111/papr.12189 · 2.18 Impact Factor