Pain relief for women undergoing oocyte retrieval for assisted reproduction

Irene Kwan; Rui Wang; Emily Pearce; Siladitya Bhattacharya

doi:10.1002/14651858.CD004829.pub4

. 2018 May 15;2018(5):CD004829. doi: 10.1002/14651858.CD004829.pub4

Pain relief for women undergoing oocyte retrieval for assisted reproduction

Irene Kwan ^1,^✉, Rui Wang ², Emily Pearce ³, Siladitya Bhattacharya ⁴

Editor: Cochrane Gynaecology and Fertility Group

PMCID: PMC6953349 PMID: 29761478

Abstract

Background

Various methods of conscious sedation and analgesia (CSA) have been used during oocyte retrieval for assisted reproduction. The choice of agent has been influenced by the quality of sedation and analgesia and by concerns about possible detrimental effects on reproductive outcomes.

Objectives

To assess the effectiveness and safety of different methods of conscious sedation and analgesia for pain relief and pregnancy outcomes in women undergoing transvaginal oocyte retrieval.

Search methods

We searched; the Cochrane Gynaecology and Fertility specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL, and trials registers in November 2017. We also checked references, and contacted study authors for additional studies.

Selection criteria

We included randomised controlled trials (RCTs) comparing different methods and administrative protocols for conscious sedation and analgesia during oocyte retrieval.

Data collection and analysis

We used standard methodological procedures expected by Cochrane. Our primary outcomes were intraoperative and postoperative pain. Secondary outcomes included clinical pregnancy, patient satisfaction, analgesic side effects, and postoperative complications.

Main results

We included 24 RCTs (3160 women) in five comparisons. We report the main comparisons below. Evidence quality was generally low or very low, mainly owing to poor reporting and imprecision.

1. CSA versus other active interventions.

All evidence for this comparison was of very low quality.

CSA versus CSA plus acupuncture or electroacupuncture

Data show more effective intraoperative pain relief on a 0 to 10 visual analogue scale (VAS) with CSA plus acupuncture (mean difference (MD) 1.00, 95% confidence interval (CI) 0.18 to 1.82, 62 women) or electroacupuncture (MD 3.00, 95% CI 2.23 to 3.77, 62 women).

Data also show more effective postoperative pain relief (0 to 10 VAS) with CSA plus acupuncture (MD 0.60, 95% CI ‐0.10 to 1.30, 61 women) or electroacupuncture (MD 2.10, 95% CI 1.40 to 2.80, 61 women).

Evidence was insufficient to show whether clinical pregnancy rates were different between CSA and CSA plus acupuncture (odds ratio (OR) 0.61, 95% CI 0.20 to 1.86, 61 women). CSA alone may be associated with fewer pregnancies than CSA plus electroacupuncture (OR 0.22, 95% CI 0.07 to 0.66, 61 women).

Evidence was insufficient to show whether rates of vomiting were different between CSA and CSA plus acupuncture (OR 1.64, 95% CI 0.46 to 5.88, 62 women) or electroacupuncture (OR 1.09, 95% CI 0.33 to 3.58, 62 women).

Trialists provided no usable data for other outcomes of interest.

CSA versus general anaesthesia

Postoperative pain relief was greater in the CSA group (0 to 3 Likert: mean difference (MD) 1.9, 95% CI 2.24 to 1.56, one RCT, 50 women).

Evidence was insufficient to show whether groups differed in clinical pregnancy rates (OR 1.00, 95% CI 0.43 to 2.35, two RCTs, 108 women, I² = 0%).

Evidence was insufficient to show whether groups differed in rates of vomiting (OR 0.46, 95% CI 0.08 to 2.75, one RCT, 50 women) or airway obstruction (OR 0.14, 95% CI 0.02 to 1.22, one RCT, 58 women). Fewer women needed mask ventilation in the CSA group (OR 0.05, 95% CI 0.01 to 0.20, one RCT, 58 women).

Evidence was also insufficient to show whether groups differed in satisfaction rates (OR 0.66, 95% CI 0.11 to 4.04, two RCTs, 108 women, I² = 34%; very low‐quality evidence).

Trialists provided no usable data for outcomes of interest.

2. CSA + paracervical block (PCB) versus other interventions.

CSA + PCB versus electroacupuncture + PCB

Intraoperative pain scores were lower in the CSA + PCB group (0 to 10 VAS: MD ‐0.66, 95% CI ‐0.93 to ‐0.39, 781 women, I² = 76%; low‐quality evidence).

Evidence was insufficient to show whether groups differed in clinical pregnancy rates (OR 0.96, 95% CI 0.72 to 1.29, 783 women, I² = 9%; low‐quality evidence).

Trialists provided no usable data for other outcomes of interest.

CSA + PCB versus general anaesthesia

Evidence was insufficient to show whether groups differed in postoperative pain scores (0 to 10 VAS: MD 0.49, 95% CI ‐0.13 to 1.11, 50 women; very low‐quality evidence).

Evidence was insufficient to show whether groups differed in clinical pregnancy rates (OR 0.70, 95% CI 0.22 to 2.26, 51 women; very low‐quality evidence).

Trialists provided no usable data for other outcomes of interest.

CSA + PCB versus spinal anaesthesia

Postoperative pain scores were higher in the CSA + PCB group (0 to 10 VAS: MD 1.02, 95% CI 0.48 to 1.56, 36 women; very low‐quality evidence).

Evidence was insufficient to show whether groups differed in clinical pregnancy rates (OR 0.93, 95% CI 0.24 to 3.65, 38 women; very low‐quality evidence).

Trialists provided no usable data for other outcomes of interest.

CSA + PCB versus PCB

Evidence was insufficient to show whether groups differed in clinical pregnancy rates (OR 0.93, 95% CI 0.44 to 1.96, 150 women; low‐quality evidence) or satisfaction (OR 1.63, 95% CI 0.68 to 3.89, 150 women, low‐quality evidence).

Trialists provided no usable data for other outcomes of interest.

CSA + PCB versus CSA only

Evidence was insufficient to show whether groups differed in clinical pregnancy rates (OR 0.62, 95% CI 0.28 to 1.36, one RCT, 100 women; very low‐quality evidence). Rates of postoperative nausea and vomiting were lower in the CS + PCB group (OR 0.42, 95% CI 0.18 to 0.97, two RCTs, 140 women, I² = 40%; very low‐quality evidence).

Trialists provided no usable data for other outcomes of interest.

Authors' conclusions

The evidence does not support one particular method or technique over another in providing effective conscious sedation and analgesia for pain relief during and after oocyte retrieval. Simultaneous use of sedation combined with analgesia such as the opiates, further enhanced by paracervical block or acupuncture techniques, resulted in better pain relief than occurred with one modality alone. Evidence was insufficient to show conclusively whether any of the interventions influenced pregnancy rates. All techniques reviewed were associated with a high degree of patient satisfaction. Women’s preferences and resource availability for choice of pain relief merit consideration in practice.

Plain language summary

Pain relief for women undergoing oocyte retrieval for assisted reproduction

Review question

Cochrane review authors investigated the effectiveness and safety of methods used for pain relief in women during transvaginal oocyte retrieval ‐ a technique used to collect eggs from the ovaries, to enable fertilisation outside the body.

Background

Conscious sedation comprises use of a drug or drugs to produce a state of relaxation enabling treatment to be carried out, during which verbal contact with the patient is maintained throughout the period of sedation. Conscious sedation and analgesia are methods used to relieve pain during surgery to retrieve eggs from the ovaries as part of in vitro (i.e. in an artificial environment such as a laboratory) fertilisation procedures. Concerns include that drugs used for sedation and pain relief may have an adverse effect on pregnancy rates.

Study characteristics

This review identified 24 randomised controlled trials, involving 3160 women, comparing the effects of five different methods of conscious sedation and pain relief including general anaesthesia. A randomised controlled trial uses research methods that aim to reduce bias when a new treatment is tested by allocating participants at random (i.e. by chance alone) to treatment or control treatment. The evidence is current to November 2017.

Key results

The evidence does not support one particular method or technique over another in providing effective conscious sedation and analgesia for pain relief during and after oocyte retrieval. Simultaneous use of sedation combined with analgesia such as the opiates, further enhanced by techniques of paracervical block or acupuncture, resulted in better pain relief than occurred with one method alone. Evidence was insufficient to show conclusively whether any of the interventions influenced pregnancy rates. All techniques reviewed were associated with a high degree of patient satisfaction. It would be appropriate to consider women’s preferences and choice of resources available for pain relief in practice.

Quality of the evidence

Evidence is generally of low or very low quality, mainly owing to poor reporting methods and small sample sizes with low event rates. As women vary in their experience of pain and awareness of coping strategies, the optimal method may be individualised.

Summary of findings

Background

Description of the condition

Transvaginal retrieval of oocytes from the ovary is a fundamental step of in vitro fertilisation (IVF) treatment. Although this approach is less invasive and of shorter duration than laparoscopic retrieval of oocytes, which is no longer common clinical practice, it remains a stressful and painful procedure, which requires analgesia and conscious sedation (Ng 2001).

Description of the intervention

Conscious sedation is defined by the American Society of Anaesthetists as “a drug‐induced depression of consciousness during which patients respond purposefully to verbal commands, either alone or accompanied by light tactile stimulation. No interventions are required to maintain a patent airway, and spontaneous ventilation is adequate. Cardiovascular function is usually maintained” (ASA 2015). Loss of consciousness should be unlikely due to the agents and techniques selected (Skelly 1996).

Analgesia is defined as “a state of reduced pain perception” (White 1987). An ideal analgesia is one that has the capability of offering pain relief without impairing consciousness.

Conscious sedation and analgesia may be combined for optimal effect. A variety of drugs and combinations thereof have been used to modify pain and anxiety during oocyte retrieval. Methods currently used to provide pain relief during transvaginal oocyte retrieval include conscious sedation, neuraxial anaesthesia (epidural or spinal), injection of local anaesthetic agents into the cervix (paracervical block), and alternative treatments such as acupuncture or electroacupuncture (Sharma 2015). General anaesthesia may be used for transvaginal oocyte retrieval; however, this approach has important resource requirements and many IVF units opt for conscious sedation and analgesia.

The primary goal of clinicians is to provide safe and effective sedation and analgesia that contribute to optimum surgical conditions and fast postoperative recovery. The aims of general and regional (epidural and spinal) anaesthesia are clear. The former renders the patient unconscious with no awareness of pain, and the latter achieves the endpoint of no sensation (of pain) while consciousness is maintained. Sedation, however, is much less clear or well defined than anaesthesia and has a smaller evidence base to guide practice. Giving too much or too little sedation can be hazardous, as too much sedation would be dangerous and too little would be ineffective. In addition, analgesics such as fentanyl and pethidine in high dosages can produce sedation, and intravenous anaesthetics such as propofol (sedative and analgesia) at subanaesthetic dosages can have sedative effects.

How the intervention might work

The pain experienced by patients during oocyte retrieval is caused by puncture of vaginal skin and the ovarian capsule by the aspirating needle and manipulation of the needle within the ovary during the procedure. It has been suggested that the pain associated with oocyte retrieval is intermittent rather than continuous (Zelcer 1992). Thus, an ideal strategy for pain relief is one that allows maximum flexibility to respond to the changing requirements of women undergoing oocyte retrieval. Patient‐controlled analgesia may facilitate an individualised approach by allowing women a degree of control over drug administration.

Acupuncture practices are based on the hypothesis that human physiological functions are controlled by Yin and Yang channels, which allow the flow of hypothetical “Qi” through the body (Han 2011). It is believed that blockage of these channels can lead to illness and pain. Insertion of acupuncture needles into specific acupuncture sites to resolve blockage and allow free flow of “Qi” is traditionally believed to relieve patient symptoms and is often used for pain relief (Han 2011).

Manual acupuncture involves insertion and manipulation of acupuncture needles within specific predetermined acupuncture sites. In electrical acupuncture, an additional current is administered through the acupuncture needles to stimulate acupoints (Zhao 2008).

Why it is important to do this review

Most oocyte retrievals are performed with the patient under conscious sedation: This approach is applied in 84% of IVF clinics in the UK (Elkington 2003), as well as 95% of IVF centres in the United States (Ditkoff 1997). However, 16% of UK clinics and about 50% of clinics in Germany have used general anaesthesia for IVF procedures (Rjosk 1993). Another survey showed that 48% of IVF clinics in the UK used conscious sedation; 29% general anaesthesia; 12% sedation combined with regional anaesthesia; and 2% regional anaesthesia; 9% offered a choice of anaesthesia for IVF procedures (Bokhari 1999). These reported variations in methods used for pain relief raise questions about the potential advantages and disadvantages of different methods and protocols for conscious sedation and analgesia. The efficacy of the various sedative‐analgesic combinations, including general anaesthesia, for women undergoing oocyte retrieval is of interest to practitioners. This systematic review aims to assess the effectiveness and safety of different methods of achieving conscious sedation and analgesia in women undergoing transvaginal oocyte retrieval, in terms of pain relief during and after the procedure, pregnancy outcomes, postoperative complications, and patient satisfaction.

Objectives

To assess the effectiveness and safety of different methods of conscious sedation and analgesia for pain relief and pregnancy outcomes in women undergoing transvaginal oocyte retrieval.

Methods

Criteria for considering studies for this review

Types of studies

We included randomised controlled trials (RCTs) only and excluded quasi‐randomised and cross‐over trials.

Types of participants

Women undergoing transvaginal oocyte retrieval during IVF treatment.

Types of interventions

Conscious sedation and analgesia versus no treatment or placebo
Conscious sedation and analgesia versus different methods such as general and spinal anaesthesia, including acupuncture and paracervical block
Different protocols of conscious sedation and analgesia such as patient‐controlled or physician‐controlled sedation

We excluded from this review trials involving the use of local anaesthesia such as vaginal lidocaine gel.

Types of outcome measures

Primary outcomes

Intraoperative pain score, defined as pain reported during or immediately after oocyte retrieval as measured on a visual analogue scale (VAS), a Likert scale, or another defined numerical or non‐numerical scale
Postoperative pain score, defined as pain reported at some time (minutes or hours) after oocyte retrieval as measured on a VAS, a Likert scale, or another defined numerical or non‐numerical scale

For the purposes of this review, we have defined postoperative pain as pain measured at some time after oocyte retrieval. In addition, none of the studies reporting pregnancy defined it, and in this review, we assumed that clinical pregnancy was reported, unless otherwise stated.

We converted to a 0 to 10 scale all VAS data related to pain.

Secondary outcomes

Live birth rate and ongoing pregnancy rate (beyond 20 weeks) per woman
Clinical pregnancy rate per woman (established by pregnancy test and confirmed by ultrasound)
Fertilisation rate per woman
Side effects of analgesia (nausea and vomiting)
Postoperative complications (airway, blood pressure, recovery time, spinal headache)
Patient satisfaction (women's reports of satisfaction with pain relief and anaesthetic care throughout the oocyte retrieval procedure)

Search methods for identification of studies

Electronic searches

We searched the Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register (Procite platform), on 11 November 2017, to identify all RCTs that compared different methods of conscious sedation and analgesia for pain control during oocyte retrieval (refer to Appendix 1), without language restriction and in consultation with the CGFG Information Specialist.

We conducted electronic searches within the following electronic databases.

CENTRAL CRSO, web platform (Appendix 2) (searched 9 November 2017).
MEDLINE, Ovid platform, (Appendix 3) (searched from 1946 to 9 November 2017).
Embase, Ovid platform (Appendix 4) (searched from 1980 to 9 November 2017).
PsycINFO, Ovid platform (Appendix 5) (searched from 1806 to 9 November 2017).
CINAHL, Ebsco platform (Appendix 6) (searched from 1982 to 9 November 2017).
ClinicalTrials.gov search strategy; web platform (Appendix 7) (searched 10 January 2017).
WHO ICTRP search strategy, web platform (Appendix 8) (searched 10 December 2016).
Web of Science, web platform (Appendix 9) (searched 12 January 2017).
Portal Regional da BVS, web platform (Appendix 10) (searched 12 January 2017).
OpenGrey, web platform (Appendix 11) (searched 12 January 2017).

Searching other resources

We searched and checked the reference lists of the included studies. We translated one article from Turkish, one from Spanish, and four from Chinese.

Data collection and analysis

Selection of studies

Three review authors (IK, EP, RW) independently examined the titles and abstracts of articles retrieved by the search and retrieved full texts of all potentially eligible studies. Each review author independently applied the selection criteria to the trial reports, resolving disagreements by discussion and, if necessary, by consultation with one other review author (SB). IK contacted trial authors for clarification of details related to study eligibility such as allocation method.

Data extraction and management

We conducted data collection and analysis in accordance with the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Three review authors (IK, EP, RW) independently extracted data from eligible studies using a data extraction form designed and pilot‐tested by the review authors. Review authors were not blinded to trial authors or journal of publication when doing this. We compared results and resolved any differences by discussion. A fourth review author (SB) resolved any disagreement that arose between these three review authors. Where information provided in the published report was insufficient, IK contacted the study authors to request further information and clarification.

Assessment of risk of bias in included studies

Three review authors (IK, EP, RW) independently assessed each trial for risk of bias according to the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

We assessed random sequence generation, concealment of allocation, blinding, completeness of outcome data (including use of intention‐to‐treat analysis), and selective outcome reporting for each trial. We also assessed other potential sources of bias. We categorised each trial as having low, unclear, or high risk of bias for each domain by applying the standards described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). When the method used to conceal allocation was not reported clearly, IK contacted the study authors for clarification.

Measures of treatment effect

For dichotomous data, we used the numbers of events in control and intervention groups of each study to calculate Mantel‐Haenszel odds ratios (ORs). For continuous data, we calculated the mean difference (MD) between treatment groups. We have presented 95% confidence intervals (CIs) for all outcomes.

Unit of analysis issues

The primary analysis was per woman randomised. For reported data that did not allow valid analysis (e.g. 'per cycle' rather than 'per woman' when women contributed more than one cycle), we computed to obtain results ‘per woman’, if possible.

Dealing with missing data

We analysed data on an intention‐to‐treat basis as far as possible, and IK contacted the trial authors to request any missing data. When no additional information was forthcoming, we assumed any missing data were the result of failure to achieve the outcome.

Assessment of heterogeneity

For each meta‐analysis, we assessed statistical heterogeneity by using I² and Chi² statistics. We determined that substantial heterogeneity was present if I² was greater than 50%, or if P < 0.10 in the Chi² test for heterogeneity (Higgins 2011). For the remaining studies, we have presented a descriptive summary of study outcomes.

Assessment of reporting biases

We planned to present a funnel plot if publication bias was questionable because some trials had not been identified (Higgins 2011), but no analysis included sufficient studies to warrant this.

Data synthesis

When appropriate, we combined dichotomous data for meta‐analysis using RevMan software and the Mantel‐Haenszel method to estimate pooled ORs with 95% CIs based on a fixed‐effect model. For continuous data, we computed weighted MDs with 95% CIs, also using a fixed‐effect model in the meta‐analysis.

We classified and analysed interventions under broad categories or strategies of pain relief, for example, types of conscious sedation and analgesia methods and administration protocols. The interventions examined were so diverse that it was not possible to quantitatively combine the results of all 24 studies. However, we were able to combine the data from four trials that compared the effects of electro‐acupuncture versus conventional medical analgesia. We also attempted meta‐analysis of the four trials comparing patient‐controlled and physician‐controlled sedation and analgesia. For the remaining studies, we have presented a descriptive summary of the outcomes of each trial.

Subgroup analysis and investigation of heterogeneity

We did not perform subgroup analysis in this review. We assessed statistical heterogeneity using the Chi² test (with P < 0.1 as evidence of significant heterogeneity) and the I² statistic (Higgins 2011).

Sensitivity analysis

We performed sensitivity analysis for the primary outcomes to assess whether findings of the analysis were robust, or whether the conclusions would have differed if eligibility was restricted to studies without high risk of bias.

Overall quality of the body of evidence: "Summary of findings" table

We prepared "Summary of findings" tables using GRADEpro and Cochrane methods (Higgins 2011). These tables evaluate the overall quality of the body of evidence for review outcomes (intraoperative pain, postoperative pain, pregnancy outcomes, side effects of analgesia (nausea and vomiting), postoperative complications, and patient satisfaction) for the main review comparisons (conscious sedation and analgesia vs other active interventions; conscious sedation and analgesia plus paracervical block vs other active interventions). We assessed the quality of evidence using the following GRADEpro criteria: risk of bias, consistency of effect, imprecision, indirectness, and publication bias. Two review authors working independently made judgements about evidence quality (high, moderate, low, or very low) and resolved disagreements by discussion. Review authors justified, documented, and incorporated judgements into reporting of results for each outcome.

Results

Description of studies

See Characteristics of included studies.

Results of the search

In the original review, our search strategy yielded 390 reports, 27 of which were potentially eligible for inclusion in the review. After full‐text review, we excluded 16 reports because conscious sedation was not one of the comparators (see Characteristics of excluded studies). Twelve papers met our inclusion criteria (Ben‐Shlomo 1999; Bhattacharya 1997; Cook 1993; Humaidan 2004; Lok 2002; Ng 2001; Ocal 2002; Ramsewak 1990; Stener‐Victorin 1999; Stener‐Victorin 2003; Thompson 2000; Zelcer 1992). These trials involved 1350 women who underwent oocyte retrieval. For the 2012 review update, we identified nine additional studies involving 1624 women (Coskun 2011; Gejervall 2005; Guasch 2005; Gunaydin 2007; Ma 2008; Meng 2008; Meng 2009; Ozturk 2006; Sator‐Katzenschlager 2006). For the 2018 review update, we identified three new studies involving 186 women (Elnabtity 2017; Lier 2014; Matsota 2012).

The study flow is shown in Figure 1.

Included studies

We included in this review a total of 24 studies involving 3160 women (see Characteristics of included studies).

Study design and setting

All 24 included studies were RCTs published between 1990 and 2017. They involved a total of 3160 women (range 30 to 700) and were conducted in Austria (N = 1), China (N = 5), Israel (N = 1), Spain (N = 1), Sweden (N = 4), the Netherlands (N = 1), Greece (N = 1), Turkey (N = 4), Eygpt (N = 1), UK (N = 4), and USA (N = 1). Two were multi‐centred trials, one involving three IVF centres (Stener‐Victorin 1999), and the other involving five IVF centres (Stener‐Victorin 2003). None of these trials reported specifically that participants included egg donors. We did not identify any quasi‐randomised or cross‐over trials.

Participants

The studies included 3160 women ‐ 1545 in control groups and 1615 in intervention groups. Two trials did not report participant age (Cook 1993; Ramsewak 1990). Overall age reported in the other studies was similar, and mean participant age was between 31 and 34 years (range 22 to 46 years). All participants were women with infertility problems due to tubal factors, endometriosis, polycystic ovary syndrome (PCOS), male factors, or unexplained infertility. Three trials reported the duration of infertility as about four to five years (Bhattacharya 1997; Elnabtity 2017; Meng 2009).

Interventions

Interventions varied substantially between studies, and review authors grouped them into five broad categories for comparison.

Conscious sedation and analgesia versus placebo (Ramsewak 1990).
Conscious sedation and analgesia versus other active interventions such as general and acupuncture anaesthesia (Ben‐Shlomo 1999; Matsota 2012; Meng 2008; Meng 2009; Sator‐Katzenschlager 2006).
Conscious sedation and analgesia plus paracervical block versus other active interventions such as general, spinal, and acupuncture anaesthesia (Gejervall 2005; Guasch 2005; Gunaydin 2007; Humaidan 2004; Ng 2001; Ozturk 2006; Stener‐Victorin 1999; Stener‐Victorin 2003).
Patient‐controlled conscious sedation and analgesia versus physician‐administered conscious sedation and analgesia (Bhattacharya 1997; Lier 2014; Lok 2002; Thompson 2000; Zelcer 1992).
Conscious sedation and analgesia with different agents or dosages (Cook 1993; Coskun 2011; Ma 2008; Ocal 2002).

Outcomes

Primary outcomes

A total of 22 studies reported intraoperative pain
In all, 11 studies reported postoperative pain (Ben‐Shlomo 1999; Elnabtity 2017; Gejervall 2005; Guasch 2005; Humaidan 2004; Lier 2014; Lok 2002; Meng 2008; Sator‐Katzenschlager 2006; Stener‐Victorin 1999; Stener‐Victorin 2003)
Two studies reported the primary outcomes of pain but did not specify whether pain was measured intraoperatively or postoperatively (Meng 2009; Thompson 2000)
Two studies did not report the primary outcomes of pain (Cook 1993; Matsota 2012)

Secondary outcomes

1/24 studies reported live birth per woman (Stener‐Victorin 1999)
2/24 studies reported ongoing pregnancy per woman (Lier 2014; Stener‐Victorin 2003)
14/24 studies reported clinical pregnancy rate per woman (Ben‐Shlomo 1999; Coskun 2011; Gejervall 2005; Guasch 2005; Humaidan 2004; Lier 2014; Lok 2002; Matsota 2012; Ng 2001; Ozturk 2006; Sator‐Katzenschlager 2006; Stener‐Victorin 1999; Stener‐Victorin 2003; Thompson 2000)
5/24 studies reported fertilisation rate per woman (Ben‐Shlomo 1999; Lok 2002; Matsota 2012; Ng 2001; Ozturk 2006)
13/24 studies reported side effects (nausea and vomiting) (Coskun 2011; Elnabtity 2017; Guasch 2005; Gunaydin 2007; Lier 2014; Ma 2008; Matsota 2012; Meng 2009; Ozturk 2006; Sator‐Katzenschlager 2006; Stener‐Victorin 1999; Stener‐Victorin 2003; Zelcer 1992)
5/24 studies reported complications (transient loss of consciousness; loss of airway) (Cook 1993; Coskun 2011; Guasch 2005; Matsota 2012; Thompson 2000)
15/24 studies reported patient satisfaction (Ben‐Shlomo 1999; Bhattacharya 1997; Cook 1993; Coskun 2011; Elnabtity 2017; Gejervall 2005; Guasch 2005; Gunaydin 2007; Lier 2014; Lok 2002; Matsota 2012; Ng 2001; Ozturk 2006; Sator‐Katzenschlager 2006; Thompson 2000)

No studies reported the incidence of abandoned procedures.

Excluded studies

See Characteristics of excluded studies.

After full‐text screening, we excluded 25 studies for the following reasons.

20/25 studies did not include conscious sedation and analgesia as a comparator.
1/25 studies did not provide clear inclusion criteria for the population and we received no response from trial authors when contacted.
1/25 studies compared conscious sedation and analgesia between different populations.
3/25 studies were abstracts, and we were unable to obtain evidence of randomisation.

Risk of bias in included studies

See Risk of bias in included studies, Figure 2, and Figure 3.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Allocation

Nineteen studies were at low risk of selection bias related to random sequence generation, as they used computer randomisation or a random numbers table. Six studies were at unclear risk of bias, as they did not describe the randomisation method used (Cook 1993; Elnabtity 2017; Gunaydin 2007; Ocal 2002; Ozturk 2006; Zelcer 1992). Eight studies did not describe allocation concealment and were at unclear risk of bias in this domain (Gejervall 2005; Guasch 2005; Lier 2014; Ma 2008; Meng 2009; Ocal 2002; Sator‐Katzenschlager 2006; Zelcer 1992).

Blinding

Blinding status could affect findings for the outcomes of pain, side effects, and women’s satisfaction. The subjective nature of pain has traditionally made it difficult to assess the efficacy of techniques for analgesia. We did not consider that blinding was likely to influence risk of performance bias for the outcomes of live birth and ongoing pregnancy. However, we noted the potential for bias for the outcomes of fertilisation and subsequent clinical pregnancy when operators were not blinded to allocation. Three studies reported adequate blinding of administrators of interventions to group allocation (Gejervall 2005; Ng 2001; Sator‐Katzenschlager 2006), and we consider these studies to be at low risk of bias. For 17 studies, blinding was not possible because of the nature of interventions such as general anaesthesia or techniques involving paracervical block (Ben‐Shlomo 1999; Bhattacharya 1997; Cook 1993; Gejervall 2005; Gunaydin 2007; Humaidan 2004; Lier 2014; Lok 2002; Matsota 2012; Meng 2008; Meng 2009; Ocal 2002; Ozturk 2006; Stener‐Victorin 1999; Stener‐Victorin 2003; Thompson 2000; Zelcer 1992), and we consider these studies to be at unclear risk of bias. Three studies described use of placebo identical to the intervention and were deemed to be at low risk of performance bias for both subjective and objective outcomes (Ng 2001; Ramsewak 1990; Sator‐Katzenschlager 2006).

Seven studies described blinding of outcome assessors for subjective outcomes of pain (Cook 1993; Gejervall 2005; Guasch 2005; Matsota 2012; Ng 2001; Sator‐Katzenschlager 2006; Zelcer 1992), and we consider these studies to be at low risk of performance bias for subjective outcomes. In one study (Coskun 2011), an independent blinded observer unaware of the women’s allocation status recorded postoperative side effects.

Incomplete outcome data

Eighteen studies analysed all or most (> 99%) randomised women, and we judged these studies to be at low risk of bias. For three studies, loss to follow‐up ranged from 4% to 20% (Lok 2002; Ramsewak 1990; Stener‐Victorin 2003). We judged these studies to be at unclear to high risk of attrition bias.

Selective reporting

All 24 studies reported outcomes prespecified in the methods section. Some outcomes such as plasma prolactin and follicular cortisol levels, sedation concentrations, recovery status, number of embryos transferred, oocyte retrieval rate, psychometric tests, and neuropeptide Y (NPY) level of follicular fluid were not of interest for this review (Cook 1993; Coskun 2011; Gejervall 2005; Guasch 2005; Gunaydin 2007; Ng 2001; Ozturk 2006); we neither extracted nor analysed these data.

Other potential sources of bias

We assessed publication bias by using a funnel plot for primary outcomes when appropriate. Ten studies did not compare causes of infertility in intervention and control groups (Ben‐Shlomo 1999; Cook 1993; Coskun 2011; Guasch 2005; Gunaydin 2007; Meng 2009; Ocal 2002; Ramsewak 1990; Thompson 2000; Zelcer 1992). Demographic details were absent from one study (Ramsewak 1990), and another study reported only women’s age (Ocal 2002). The risk of bias related to potential baseline differences between the two groups in these studies cannot be established, and we consider these studies to be at unclear risk of bias. In one study, women in the control group were younger than those in the intervention groups, although the cause of infertility was similar between groups (Lok 2002). We found no additional potential sources of other bias in the remaining studies.

Effects of interventions

See: Table 1; Table 2; Table 3; Table 4; Table 5; Table 6; Table 7; Table 8

Summary of findings for the main comparison. Conscious sedation and analgesia (CSA) compared with CSA+acupuncture for women undergoing oocyte retrieval for assisted reproduction.

Conscious sedation and analgesia (CSA) compared with CSA+acupuncture for women undergoing oocyte retrieval for assisted reproduction
Patient or population: women undergoing oocyte retrieval for assisted reproduction  Setting: assisted reproduction clinic  Intervention: conscious sedation and analgesia (CSA)  Comparison: CSA + acupuncture
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect  (95% CI)	No. of participants  (studies)	Quality of the evidence  (GRADE)	Comments
Outcomes	Risk with CSA + acupuncture	Risk with CSA only (95% CI)	Relative effect  (95% CI)	No. of participants  (studies)	Quality of the evidence  (GRADE)	Comments
Intraoperative pain	Mean intraoperative pain score in the comparison group was 4.9 points on a 0 to 10 VAS.	Mean score in the CSA‐only group was 1 point higher  (0.18 higher to 1.82 higher)	‐	62  (1 RCT)	⊕⊝⊝⊝  VERY LOW^a,b
Postoperative pain	Mean postoperative pain score in the comparison group was 3.2 on a 0 to 10 VAS.	Mean score in the CSA‐only group was 0.6 points higher  (0.1 lower to 1.3 higher)	‐	61  (1 RCT)	⊕⊝⊝⊝  VERY LOW^a,b
Pregnancy	344 per 1000	242 per 1000 (95 to 493)	OR 0.61 (0.20 to 1.86)	61  (1 RCT)	⊕⊝⊝⊝  VERY LOW^a,b
Patient satisfaction	No studies reported this outcome.		Not estimable	‐	‐
Side effects (postoperative vomiting and/or vomiting)	156 per 1000	233 per 1000  (78 to 521)	OR 1.64  (0.46 to 5.88)	62  (1 RCT)	⊕⊝⊝⊝  VERY LOW^a,b
Postoperative complications	No studies reported this outcome.		Not estimable	‐	‐
*The risk in the intervention group (and its 95% confidence interval) is based on the risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: confidence interval; CSA: conscious sedation and analgesia; OR: odds ratio; VAS: visual analogue scale.
GRADE Working Group grades of evidence.  High quality: We are very confident that the true effect lies close to that of the estimate of the effect.  Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.  Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.  Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

Date	Event	Description
5 February 2018	New citation required but conclusions have not changed	The addition of 3 new studies has not led to any change in the conclusions of this review.
5 February 2018	New search has been performed	The review has been updated.

Date	Event	Description
1 November 2012	New search has been performed	Review title changed to "Pain relief for women undergoing oocyte retrieval for assisted reproduction" Following peer review, the primary outcomes have been changed to intra‐operative pain and post‐operative pain, and the secondary outcomes now include live birth rate.
1 November 2012	New citation required and conclusions have changed	New studies added with change to conclusions
25 July 2012	New search has been performed	New search performed. Nine new RCTs added to the review: Coskun 2011; Gejervall 2005; Guasch 2005; Gunaydin 2007; Ma 2008; Meng 2008; Meng 2009; Ozturk 2006; Sator‐Katzenschlager 2006
23 May 2005	Feedback has been incorporated	Substantive amendment

#	Query	Results
S33	S8 AND S32	161
S32	S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18 OR S19 OR S20 OR S21 OR S22 OR S23 OR S24 OR S25 OR S26 OR S27 OR S28 OR S29 OR S30 OR S31	198,907
S31	TX bolus N2 injection*	593
S30	TX opioid*	24,706
S29	TX anaesthe* or anesthe*	105,222
S28	TX pethidine	340
S27	TX paracervical block*	56
S26	TX electroacupuncture or TX acupuncture	16,899
S25	(MM "Electroacupuncture")	830
S24	(MM "Patient‐Controlled Analgesia")	1,146
S23	(MM "Acupuncture Analgesia") OR (MM "Acupuncture Anesthesia") OR (MM "Anesthesia and Analgesia+")	42,145
S22	TX medazepam or TX lorazepam	981
S21	TX analgesi*	43,331
S20	TX hypnotic*	6,770
S19	(MM "Hypnotics and Sedatives+")	8,371
S18	(MH "Analgesia")	5,172
S17	TX (propofol or ketamine or isoflurane)	9,783
S16	TX diazepam or TX midazolam	4,403
S15	TX fentanyl	4,682
S14	(MH "Alfentanil") OR TX "alfentanil"	517
S13	TX"bolus injection*"	516
S12	TX"pain relief"	10,689
S11	(MM "Sedation") OR TX "sedation"	11,628
S10	(MH "Narcotics+") OR TX"narcotics" OR (MH "Analgesics, Opioid+")	35,974
S9	(MM "Conscious Sedation") OR TX"Conscious Sedation"	2,912
S8	S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7	4,291
S7	TX follicle aspiration*	14
S6	(MH "Oocyte Donation") OR "oocyte donation"	517
S5	TX oocyte collection*	14
S4	TX egg pick up	2
S3	TX oocyte retrieval*	150
S2	TX ICSI	429
S1	(MH "Fertilization in Vitro") OR "ivf"	3,762

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Pain during needle insertion (VAS 0 to 10)	1	24	Mean Difference (IV, Fixed, 95% CI)	‐1.70 [‐2.38, ‐1.02]
2 Pain during follicle aspiration (VAS 0 to 10)	1	24	Mean Difference (IV, Fixed, 95% CI)	‐1.30 [‐1.88, ‐0.72]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Intraoperative pain	2		Mean Difference (IV, Random, 95% CI)	Subtotals only
1.1 CSA vs CSA + acupuncture (VAS 0 to 10)	1	62	Mean Difference (IV, Random, 95% CI)	1.0 [0.18, 1.82]
1.2 CSA vs CSA + electro‐acupuncture (VAS 0 to 10)	1	62	Mean Difference (IV, Random, 95% CI)	3.00 [2.23, 3.77]
1.3 CSA vs CSA + electro‐acupuncture (Pain scale 1 to 12)	1	316	Mean Difference (IV, Random, 95% CI)	1.70 [1.07, 2.33]
2 Postoperative pain	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
2.1 CSA vs CSA + acupuncture (VAS 0 to 10)	1	61	Mean Difference (IV, Fixed, 95% CI)	0.60 [‐0.10, 1.30]
2.2 CSA vs CSA + electro‐acupuncture (VAS 0 to 10)	1	61	Mean Difference (IV, Fixed, 95% CI)	2.1 [1.40, 2.80]
2.3 CSA vs general anaesthesia (Likert 0 to 3)	1	50	Mean Difference (IV, Fixed, 95% CI)	‐1.90 [‐2.24, ‐1.56]
3 Pregnancy	3		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
3.1 CSA vs CSA + acupuncture	1	61	Odds Ratio (M‐H, Fixed, 95% CI)	0.61 [0.20, 1.86]
3.2 CSA vs CSA + electro‐acupuncture	1	61	Odds Ratio (M‐H, Fixed, 95% CI)	0.22 [0.07, 0.66]
3.3 CSA vs general anaesthesia	2	108	Odds Ratio (M‐H, Fixed, 95% CI)	1.0 [0.43, 2.35]
4 Postop vomiting and/or vomiting	2		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
4.1 CSA vs CSA + acupuncture	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.2 CSA vs general anaesthesia	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Satisfaction	2		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
5.1 CSA vs general anaesthesia	2	108	Odds Ratio (M‐H, Fixed, 95% CI)	0.66 [0.11, 4.04]
6 Postoperative complications (airway obstruction)	1	58	Odds Ratio (M‐H, Fixed, 95% CI)	0.14 [0.02, 1.22]
6.1 CSA vs general anaesthesia	1	58	Odds Ratio (M‐H, Fixed, 95% CI)	0.14 [0.02, 1.22]
7 Postoperative complications (mask ventilation)	1	58	Odds Ratio (M‐H, Fixed, 95% CI)	0.05 [0.01, 0.20]
7.1 CSA vs general anaesthesia	1	58	Odds Ratio (M‐H, Fixed, 95% CI)	0.05 [0.01, 0.20]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Intraoperative pain (VAS 0 to 10)	4		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
1.1 CSA + paracervical block versus electro‐acupuncture + paracervical block	4	781	Mean Difference (IV, Fixed, 95% CI)	‐0.66 [‐0.93, ‐0.39]
2 Postoperative pain	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
2.1 CSA + paracervical block vs general anaesthesia	1	50	Mean Difference (IV, Fixed, 95% CI)	0.49 [‐0.13, 1.11]
2.2 CSA + paracervical block vs spinal anaesthesia	1	36	Mean Difference (IV, Fixed, 95% CI)	1.02 [0.48, 1.56]
3 Live birth or ongoing pregnancy	2	393	Odds Ratio (M‐H, Fixed, 95% CI)	1.20 [0.78, 1.86]
3.1 CSA + paracervical block vs electro‐acupuncture + paracervical block	1	149	Odds Ratio (M‐H, Fixed, 95% CI)	2.35 [1.09, 5.05]
3.2 CSA + paracervical block vs electro‐acupuncture + paracervical block	1	244	Odds Ratio (M‐H, Fixed, 95% CI)	0.86 [0.50, 1.47]
4 Pregnancy	7		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
4.1 CSA + paracervical block vs general anaesthesia	1	51	Odds Ratio (M‐H, Fixed, 95% CI)	0.70 [0.22, 2.26]
4.2 CSA + paracervical block vs spinal anaesthesia	1	38	Odds Ratio (M‐H, Fixed, 95% CI)	0.93 [0.24, 3.65]
4.3 CSA + paracervical block vs paracervical block only	1	150	Odds Ratio (M‐H, Fixed, 95% CI)	0.93 [0.44, 1.96]
4.4 CSA + paracervical block vs electro‐acupuncture + paracervical block	4	783	Odds Ratio (M‐H, Fixed, 95% CI)	0.96 [0.72, 1.29]
4.5 CSA + paracervical block vs CSA alone	1	100	Odds Ratio (M‐H, Fixed, 95% CI)	0.62 [0.28, 1.36]
5 Fertilisation rate per woman	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
5.1 CSA + paracervical block vs paracervical block only	1	150	Odds Ratio (M‐H, Fixed, 95% CI)	0.83 [0.42, 1.66]
6 Postoperative nausea and/or vomiting	2		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
6.1 CSA + paracervical block vs CS only	2	140	Odds Ratio (M‐H, Fixed, 95% CI)	0.42 [0.18, 0.97]
7 Patient satisfaction by Likert scale: report of 'excellent and satisfactory'	1	150	Odds Ratio (M‐H, Fixed, 95% CI)	1.63 [0.68, 3.89]
7.1 CSA + paracervical block vs paracervical block only	1	150	Odds Ratio (M‐H, Fixed, 95% CI)	1.63 [0.68, 3.89]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Intraoperative pain score (VAS 0 to 10)	4		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
1.1 Pt‐controlled vs physician‐controlled CSA	4	379	Mean Difference (IV, Fixed, 95% CI)	0.60 [0.16, 1.03]
2 Intraoperative pain score excluding inhalational sedation/analgesia (VAS 0 to 10)	3	267	Mean Difference (IV, Fixed, 95% CI)	0.47 [‐0.01, 0.95]
2.1 Pt‐controlled vs physician‐controlled CSA	3	267	Mean Difference (IV, Fixed, 95% CI)	0.47 [‐0.01, 0.95]
3 Postoperative pain score (VAS 0 to 10)	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
3.1 Pt‐controlled vs physician‐controlled CSA	1	106	Mean Difference (IV, Fixed, 95% CI)	1.2 [0.26, 2.14]
4 Pregnancy rate per woman	3		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
4.1 Pt‐controlled vs physician‐controlled CSA	3	294	Odds Ratio (M‐H, Fixed, 95% CI)	0.90 [0.51, 1.60]
5 Fertilisation rate per woman	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
5.1 Pt‐controlled vs physician‐controlled CSA	1	106	Odds Ratio (M‐H, Fixed, 95% CI)	1.17 [0.54, 2.50]
6 Postoperative nausea: no. of patients	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
6.1 Pt‐controlled vs physician‐controlled CSA	1	80	Odds Ratio (M‐H, Fixed, 95% CI)	1.0 [0.19, 5.28]
7 Patient satisfaction by LIkert scale: report of 'very and moderately satisfied'	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
7.1 Pt‐controlled vs physician‐controlled CSA	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	1.95 [0.34, 11.28]
8 Patient satisfaction (VAS 0 to 10)	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
8.1 Pt‐controlled vs physician‐controlled CSA	1	106	Mean Difference (IV, Fixed, 95% CI)	0.20 [‐0.64, 1.04]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Intraoperative pain score at 5 minutes (VAS 0 to 10)	1	52	Mean Difference (IV, Fixed, 95% CI)	‐0.74 [‐1.48, 0.00]
2 Intraoperative pain score at 10 minutes (VAS 0 to 10)	1	52	Mean Difference (IV, Fixed, 95% CI)	‐0.90 [‐1.64, ‐0.16]
3 Postoperative pain score at 20 minutes (VAS 0 to 10)	1	52	Mean Difference (IV, Fixed, 95% CI)	0.42 [‐0.04, 0.88]
4 Patient satisfaction rate	2		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
4.1 CSA with propofol vs CSA with midazolam	1	47	Odds Ratio (M‐H, Fixed, 95% CI)	0.42 [0.04, 4.94]
4.2 CSA with dexmedetomidine vs CSA with midazolam (very satisfied)	1	52	Odds Ratio (M‐H, Fixed, 95% CI)	3.07 [0.98, 9.59]

Methods	Randomisation: random numbers Allocation concealment: sealed in consecutive envelopes Blinding of participants/investigators: no Blinding of assessors: no No. randomised: 50 No. analysed: 50 Intention‐to‐treat analysis: yes Power and sample calculations not described Duration of trial: not stated
Participants	Women scheduled for oocyte retrieval Mean age: 34 years; cause of infertility not reported Similar baseline characteristics of age, height, and weight
Interventions	Control: conscious sedation and analgesia with IV midazolam 0.06 mg followed after 2 minutes by ketamine 0.75 mg/kg (N = 25) Intervention: general anaesthesia with IV fentanyl 0.017 mg/kg followed after 2 minutes by IV propofol 2.5 mg/kg (N = 25) No premedication in either group
Outcomes	Primary: postoperative pain (Likert scale 0 to 3; 0 = none; 3 = severe) Secondary: clinical pregnancy rate, fertilisation rate, satisfaction (Likert scale 0 to 3) Other outcomes reported: no. of oocytes retrieved, cleavage rate, arousability, response to painful stimuli
Notes	Israel Single centre HaEmek Mecical Centre Funding: not stated Definition of pregnancy not documented
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random numbers
Allocation concealment (selection bias)	Low risk	Adequate: sealed envelopes
Blinding (performance bias and detection bias)   All outcomes	Unclear risk	Blinding not possible because of the nature of the interventions Blinding of assessors not reported
Incomplete outcome data (attrition bias)   All outcomes	Low risk	No apparent dropout
Selective reporting (reporting bias)	Low risk	All pre‐stated outcomes reported
Other bias	Unclear risk	Comparable baseline characteristics of age, height, and weight but not cause of infertility

Methods	Randomisation: computer‐generated random numbers Allocation concealment: sealed in consecutively numbered envelopes Blinding of participants/investigators: no Blinding of assessors: no No. randomised: 81 No. analysed: 81 Intention‐to‐treat analysis: yes Power and sample calculations described Duration of trial: not stated
Participants	Women undergoing vaginal oocyte recovery Mean age: 33 years Mean duration of infertility 5.5 years; 26% tubal disease Similar baseline demographic and infertility characteristics
Interventions	Control: patient‐controlled sedation and analgesia (IV fentanyl 200 µg) via patient‐controlled sedation and analgesia (PCS) machine (N = 39) Intervention: intermittent physician‐administered sedation and analgesia (PAS) (IV fentanyl 200 µg) (N = 42) All women received a preliminary IV loading dose of midazolam 4 mg.
Outcomes	Primary: intraoperative pain score (VAS 1 to 100) Secondary: patient satisfaction Other outcomes reported: perioperative blood pressure, pulse, oxygen, doses of fentanyl
Notes	Scotland Single centre Aberdeen University Funding: not stated
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation
Allocation concealment (selection bias)	Low risk	Adequate: sealed numbered envelopes
Blinding (performance bias and detection bias)   All outcomes	Unclear risk	Blinding not possible because of the nature of the interventions Blinding of assessors not reported
Incomplete outcome data (attrition bias)   All outcomes	Low risk	No loss to follow‐up
Selective reporting (reporting bias)	Low risk	All prespecified outcomes reported
Other bias	Low risk	Comparable demographic and infertility characteristics at baseline

Methods	Randomisation: method unclear Allocation concealment: sealed envelopes Blinding of participants/investigators: no Blinding of assessors: yes No. randomised: 47 No. analysed: 47 Intention‐to‐treat analysis: yes Power and sample calculations: not reported Duration of trial: not stated
Participants	Women presenting for transvaginal oocyte retrieval Mean age and weight similar in both groups (no data given) Cause of infertility: not reported Comparison of baseline characteristics: age/weight only
Interventions	Control: patient‐controlled sedation and analgesia infusion (propofol 300 mg in 30 mL) via a pump (N = 25) Intervention: patient‐controlled sedation and analgesia infusion (midazolam 300 mg in 30 mL) via a pump (N = 22) IV alfentanil administered at 3 points: before insertion of vaginal speculum, before needle entry into each ovary, on request
Outcomes	Secondary: patient satisfaction (VAS), adverse outcomes Other outcomes reported: sedation levels, psychometric tests
Notes	England Single centre London University Funding: not stated
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Methods unclear
Allocation concealment (selection bias)	Low risk	Adequate, sealed envelopes
Blinding (performance bias and detection bias)   All outcomes	Unclear risk	Blinding not feasible because of the different appearance of drugs Assessors blind
Incomplete outcome data (attrition bias)   All outcomes	Low risk	No loss to follow‐up
Selective reporting (reporting bias)	Low risk	All prespecified outcomes reported
Other bias	Unclear risk	Comparable baseline characteristics of age and weight but not cause of infertility

Methods	Randomisation: computer‐generated Allocation concealment: quote "enclosed" numbers Blinding of participants/investigators: no Blinding of assessors: yes (for postop side effects) No. randomised: 69 No. analysed: 69 Intention‐to‐treat analysis: yes Power and sample calculations: described Duration of trial: not stated
Participants	Women scheduled for transvaginal oocyte retrieval Mean age: 33 to 35 years Cause of infertility: not reported Comparison of baseline characteristics: age, weight, and height only Similar demographic characteristics at baseline
Interventions	Control: TCI (target‐controlled infusion) propofol 1% plus remifentanil 1.5 ng/mL (N = 23) Intervention I: TCI propofol 1% plus remifentanil 2 ng/mL (N = 23) Intervention II: TCI propofol 1% plus remifentanil 2.5 ng/mL (N = 23) TCI = A system that maintains a particular target plasma drug concentration via standard pharmacokinetic equations
Outcomes	Primary: intraoperative pain score (0 to 10‐point numerical rating scale) Secondary: pregnancy rate, side effects, satisfaction Other outcomes reported: sedation score, amount of sedation required, recovery score, blood pressure
Notes	Turkey Single centre Gazi University Funding: not stated
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation
Allocation concealment (selection bias)	Low risk	Quote "enclosed" numbers
Blinding (performance bias and detection bias)   All outcomes	Unclear risk	Blinding not reported Blinding of assessors for postop side effects only
Incomplete outcome data (attrition bias)   All outcomes	Low risk	No loss to follow‐up
Selective reporting (reporting bias)	Low risk	All prespecified outcomes reported
Other bias	Unclear risk	Comparable baseline characteristics of age, height, and weight but not cause of infertility

Methods	Ransomisation: method unclear Allocation concealment: serially numbered, sealed opaque envelopes Blinding of participants/investigators: yes Blinding of assessors: not reported No. randomised: 52 No. analysed: 52 Intention‐to‐treat analysis: awaiting response from trial author Power and sample calculations described Duration of trial: from September 2014 to April 2015
Participants	Women with ASA I/II undergoing ultrasound‐guided oocyte retrieval in an IVF programme Mean age: 25 to 38 years Cause of infertility: tubal disease, endometriosis, anovulation, male factor, unexplained Similar demographic (age, height, weight, BMI) and infertility characteristics at baseline Inclusion criteria: women in their first IVF cycle and showing bilateral ovarian follicular response Exclusion criteria: psychological abnormalities; cardiorespiratory, renal, or liver disease; requesting general anaesthesia; fewer than 3 dominant follicles present in either ovary; chronic alcohol/drug abusers; allergic to any of the medications used in the study
Interventions	1. Intervention 1: IV fentanyl (1 µg/kg) plus paracervical block (100 mg lidocaine 1%) plus IV dexmedetomidine (1 µg/kg) (N = 26) 2. Intervention 2: IV fentanyl (1 µg/kg) plus paracervical block (100 mg lidocaine 1%) plus IV midazolam (0.06 mg/kg) (N = 26)
Outcomes	Primary: intraoperative and postoperative pain scores (VAS 0 to 100) Secondary: pregnancy rate per embryo transfer, side effects of analgesia, postop complications, patient satisfaction (Likert scale) Other outcomes reported: intraoperative vital signs, no. of oocytes obtained, embryos transferred per woman, amount of rescue propofol used
Notes	Egypt University Hospital No funding received
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Method unclear
Allocation concealment (selection bias)	Low risk	Adequate: serially numbered and sealed opaque envelopes
Blinding (performance bias and detection bias)   All outcomes	Unclear risk	Double‐blind (investigators and participants) Blinding of assessors not reported
Incomplete outcome data (attrition bias)   All outcomes	Low risk	No losses to follow‐up
Selective reporting (reporting bias)	Low risk	All prespecified outcomes reported
Other bias	Low risk	Comparable demographic and infertility characteristics at baseline

Methods	Randomisation: computer‐generated list Allocation concealment: unclear Blinding of participants/investigators: yes Blinding of assessors: yes No. randomised: 160 No. analysed: 158 Intention‐to‐treat analysis: reported both as intention‐to‐treat and ‘as per protocol’ Power and sample calculations described Duration of trial: 19 months, from March 2002 to October 2003
Participants	Women undergoing oocyte aspiration Mean age: 33 to 34 years (range 23 to 39 years) Cause of infertility: tubal factor, hormonal factor, endometriosis, male factor, unexplained Similar demographic and infertility characteristics at baseline
Interventions	In a 1:1 ratio, Control: conventional sedation and analgesia (IV alfentanil 0.5 mg) plus paracervical block (lidocaine 0.5%) (N = 80) Intervention: electro‐acupuncture plus paracervical block (lidocaine 0.5%) (N = 80) Control group received premedication (oral flunitrazepam 0.5 mg and rectal paracetamol 1 g); EA group did not receive premedication.
Outcomes	Primary: intraoperative and postoperative pain scores (VAS 0 to 100) Secondary: pregnancy rate, patient satisfaction (VAS 0 to 100) Other outcomes reported: well‐being, number of embryos transferred, pregnancy per cycle
Notes	Sweden Single centre University Hospital Goteborg Funding: Research & Development Council, Goteborg and Bohuslan, the Hjarmar Sevensson Foundation, the Organon Foundation, the Wilhelm & Marina Lundgren's Foundation Loss to follow‐up (N = 2) in intervention group due to ovulation before aspiration and missing VAS assessment Definition of pregnancy not documented
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer randomisation
Allocation concealment (selection bias)	Unclear risk	Methods unclear
Blinding (performance bias and detection bias)   All outcomes	Low risk	Blinding of participants not feasible owing to the nature of the intervention Person who assessed the VAS blinded to the groups to which participants belonged Other midwives not involved in administering EA assisted in the analgesia procedure during oocyte retrieval.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Two lost to follow‐up. Data available for intention‐to‐treat and ‘per protocol’
Selective reporting (reporting bias)	Low risk	All prespecified outcomes reported
Other bias	Low risk	Comparable demographic and infertility characteristics at baseline

Methods	Randomisation: computer generation Allocation concealment: method unclear Blinding of participants/investigators: no Blinding of assessors: yes No. randomised: 65 No. analysed: 65 (IVF outcomes); 45 (satisfaction) Intention‐to‐treat analysis: yes for IVF outcomes, no for satisfaction outcomes Power and sample calculations not reported Duration of trial: 18 months, from March 1999 to September 2002
Participants	Women undergoing oocyte retrieval Age range 24 to 39 years Cause of infertility: not reported Similar baseline characteristics of age/height/weight
Interventions	Control: conscious sedation and analgesia (IV alfentanil 10 µg/kg ^‐1 and midazolam 0.06 mg/kg ^‐1 plus paracervical block (lidocaine 1.5%)) (N = 24) Intervention group 1: general anaesthesia (IV alfentanil 10 µg/kg ^‐1) (N = 27) Intervention group 2: spinal anaesthesia (N = 14) No premedication given to any groups
Outcomes	Primary: intraoperative and postoperative pain (VAS 0 to 100) Secondary: pregnancy rate, patient satisfaction (%), side effects, adverse effects Other outcomes reported: serum prolactin levels, follicular cortisol levels, oocyte recovery rate
Notes	Spain Single centre Hospital Universitario La Paz, Madrid Funding: not stated Definition of pregnancy not documented Fourth group (non‐randomised) receiving remifentanil: data not used for the review Paper in Spanish
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation
Allocation concealment (selection bias)	Unclear risk	Methods unclear
Blinding (performance bias and detection bias)   All outcomes	Unclear risk	Blinding not possible owing to the nature of the interventions Analysis conducted by an independent person not involved in the trial Oocyte and fertilisation data collected by a blinded investigator
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Complete for pain but incomplete for satisfaction
Selective reporting (reporting bias)	Low risk	All prespecified outcomes reported
Other bias	Unclear risk	Comparable baseline characteristics of age, height, and weight but not cause of infertility

Methods	Randomisation: methods unclear Allocation concealment: sealed envelopes Blinding of participants/investigators: no Blinding of assessors: no No. randomised: 40 No. analysed: 40 Intention‐to‐treat analysis: yes Power and sample calculations briefly described Duration of trial: not stated
Participants	Women scheduled to undergo transvaginal oocyte retrieval Mean age: 32 to 33 years Cause of infertility: not reported Similar baseline characteristics of age, height, and weight
Interventions	Control: conscious sedation and analgesia (IV remifentanil 2 mg in 20 mL saline) (N = 20) Intervention: conscious sedation and analgesia (IV remifentanil 2 mg in 20 mL saline) and paracervical block (lidocaine 1%) (N = 20)
Outcomes	Primary: intraoperative pain score (visual numerical scale (VAS): 0 = no pain; 10 = severe pain) Secondary: side effects, patient satisfaction (good, moderate, or bad) Other outcomes reported: plasma remifentanil levels, pulmonary function
Notes	Turkey Single centre Gazi University Funding: not stated
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Methods unclear
Allocation concealment (selection bias)	Low risk	Closed envelope allocation
Blinding (performance bias and detection bias)   All outcomes	Unclear risk	Not reported
Incomplete outcome data (attrition bias)   All outcomes	Low risk	No loss to follow‐up
Selective reporting (reporting bias)	Low risk	All prespecified outcomes reported
Other bias	Unclear risk	Comparable baseline characteristics of age, height, and weight but not cause of infertility

Methods	Randomisation: random numbers table Allocation concealment: methods unclear Blinding of participants/investigators: no Blinding of assessors: no No. randomised: 80 No. analysed: 80 Intention‐to‐treat analysis: yes Power and sample calculations not described Duration of trial: 8 months from February to September 2006
Participants	Women undergoing oocyte retrieval Mean age: 31 to 33 years Cause of infertility: tubal disease, PCOS, endometriosis, male factor, unexplained Similar demographic and infertility characteristics at baseline
Interventions	Control: conscious sedation and analgesia (iv midazolam combined with fentanyl 3.5 µg/kg) (N = 40) Intervention: conscious sedation and analgesia (iv propofol combined with fentanyl 3.5 µg/kg) (N = 40)
Outcomes	Primary: intraoperative pain score (minimal, moderate, and severe) Secondary: side effects Other outcomes reported: changes in blood pressure
Notes	China Single centre Zhejiang University, Hangzhou, China Funding: not stated Paper in Chinese
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation table
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding (performance bias and detection bias)   All outcomes	Unclear risk	Not reported
Incomplete outcome data (attrition bias)   All outcomes	Low risk	No loss to follow‐up
Selective reporting (reporting bias)	Low risk	All prespecified outcomes reported
Other bias	Low risk	Comparable demographic and infertility characteristics at baseline

Methods	Randomisation: group allocation envelopes randomly selected by co‐investigators (additional information from trial author) Allocation concealment: group allocations in sealed envelopes kept in locked office (additional information from trial author) Blinding of participants/investigators: no, owing to the nature of the intervention Blinding of assessors: yes, assessors blind to group allocation (additional information from trial author) No. randomised: 58 No. analysed: 58 Intention‐to‐treat analysis: yes Power and sample calculations not described Duration of trial: not stated
Participants	Women scheduled for ultrasound transvaginal oocyte retrieval Mean age 34 to 35.5 years Mean body weight: 62 kg Cause of infertility: 51 cases of primary infertility, 7 cases of secondary infertility Similar demographic and infertility characteristics at baseline
Interventions	1. Control: conscious sedation/analgesia with remifentanil (a bolus dose 1 μg.kg ^‐1 of remifentanil administered slowly during 1 minute following by a continuous IV infusion at a rate of 0.15 to 0.4 μg.kg ^‐1.min ^‐1) (N = 29) 2. Intervention: general anaesthesia with IV propofol 2 mg.kg^‐1 and alfentanil 15 μg.kg ^‐1, maintained with propofol continuous infusion at a rate of 2 to 4 mg.kg ^‐1.h ^‐1 (N = 29). All participants unpremedicated and received midazolam 2 mg IV just before start of the procedure
Outcomes	Secondary: clinical pregnancy rate, fertilisation rate, side effects, postoperative complications, patient satisfaction Other outcomes reported: implantation and cleavage rates
Notes	Greece Single centre University Hospital Funding: not stated Definition of pregnancy: over 16 weeks of gestation
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Group allocation envelopes randomly selected by co‐investigators
Allocation concealment (selection bias)	Low risk	Group allocations in sealed envelopes kept in locked office (additional information from trial author)
Blinding (performance bias and detection bias)   All outcomes	Unclear risk	Blinding not possible owing to the nature of the interventions Blinding of assessors not reported
Incomplete outcome data (attrition bias)   All outcomes	Low risk	No apparent loss to follow‐up
Selective reporting (reporting bias)	Low risk	All prespecified outcomes reported
Other bias	Low risk	Comparable demographic and infertility characteristics at baseline

Methods	Randomisation: random number table Allocation concealment: methods unclear Blinding of participants/investigators: no Blinding of assessors: no No. randomised: 700 No. analysed: 694 Intention‐to‐treat analysis: no Power and sample calculations not reported Duration of trial: 8 months, from June 2007 to January 2008
Participants	Women undergoing transvaginal oocyte retrieval Mean age: 30 to 31 years Cause of infertility: not reported, duration of infertility < 5 years Similar demographic and infertility characteristics at baseline
Interventions	Control: conscious sedation and analgesia (IM Dolantin 50 mg) (N = 353) Intervention: conscious sedation and analgesia (IM Dolantin 50 mg) plus electro‐acupuncture (N = 347)
Outcomes	Primary: pain (unclear whether intraoperative or postoperative) according to pain thresholds
Notes	China Single centre Nanjing University of TCM Funding: not stated No reason given for dropout (N = 6) Paper in Chinese
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation table
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding (performance bias and detection bias)   All outcomes	Unclear risk	Blinding not possible owing to the nature of the interventions Blinding of assessors not reported
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Six lost to follow‐up (2 in control group; 4 in intervention group), no reason given
Selective reporting (reporting bias)	Low risk	All prespecified outcomes reported
Other bias	Low risk	Comparable demographic and infertility characteristics at baseline

Methods	Randomisation: by pharmacy Allocation concealment: sealed envelopes kept in medicine cupboard Blinding of participants/investigators: yes Blinding of assessors: no No. randomised: 30 No. analysed: 24 Intention‐to‐treat analysis: no Power and sample calculations not reported Duration of trial: 1 month, July 1989
Participants	Women undergoing follicular aspiration Mean age: not reported Cause of infertility: not reported Baseline characteristics comparison not reported
Interventions	Control: conscious sedation and analgesia (placebo of IV normal saline) (N = 12) Intervention: conscious sedation and analgesia (IV fentanyl 100 µg) (N = 12)
Outcomes	Primary: intraoperative pain (VAS)
Notes	England Single centre Sheffield Univerity Funding: not stated 6 women (20%) excluded after randomisation  2 – transvaginal aspiration inaccessible  2 ‐ spontaneous rupture of follicle before needle insertion  1 ‐ failure to complete VAS score sheet  1 ‐ ampoule accidentally broken
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation by pharmacy
Allocation concealment (selection bias)	Low risk	Adequate: sealed envelope
Blinding (performance bias and detection bias)   All outcomes	Unclear risk	Neither medical and nursing personnel nor the patient knew which ampoule was used Blinding of assessors not reported
Incomplete outcome data (attrition bias)   All outcomes	High risk	6 women (20%) lost to follow‐up, reasons given
Selective reporting (reporting bias)	Low risk	All prespecified outcomes reported
Other bias	Unclear risk	Baseline demographic and infertility characteristics comparison not reported

PERMALINK

Pain relief for women undergoing oocyte retrieval for assisted reproduction

Irene Kwan

Rui Wang

Emily Pearce

Siladitya Bhattacharya

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Background

Description of the condition

Description of the intervention

How the intervention might work

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Types of outcome measures

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

Measures of treatment effect

Unit of analysis issues

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

Overall quality of the body of evidence: "Summary of findings" table

Results

Description of studies

Results of the search

1.

Included studies

Study design and setting

Participants

Interventions

Outcomes

Primary outcomes

Secondary outcomes

Excluded studies

Risk of bias in included studies

2.

3.

Allocation

Blinding

Incomplete outcome data

Selective reporting

Other potential sources of bias

Effects of interventions

Summary of findings for the main comparison. Conscious sedation and analgesia (CSA) compared with CSA+acupuncture for women undergoing oocyte retrieval for assisted reproduction.

Summary of findings 2. Conscious sedation and analgesia (CSA) compared with CSA + electro‐acupuncture for women undergoing oocyte retrieval for assisted reproduction.

Summary of findings 3. Conscious sedation and analgesia compared with general analgesia for women undergoing oocyte retrieval for assisted reproduction.

Summary of findings 4. Conscious sedation and analgesia (CSA) + paracervical block (PCB) versus electro‐acupuncture + PCB.

Summary of findings 5. Conscious sedation and analgesia (CSA) + paracervical block (PCB) versus general anaesthesia.

Summary of findings 6. Conscious sedation and analgesia (CSA) + paracervical block (PCB) versus spinal anaesthesia.

Summary of findings 7. Conscious sedation and analgesia (CSA) + paracervical block (PCB) versus PCB.

Summary of findings 8. Conscious sedation and analgesia (CSA) + paracervical block (PCB) versus CSA.

1. Conscious sedation and analgesia versus placebo

Primary outcome

1.1 Intraoperative pain

1.1. Analysis.

1.2. Analysis.

Methods	Randomisation: in blocks of 20 to each group, random numbers table Allocation concealment: sealed unlabelled envelopes Blinding of participants/investigators: no Blinding of assessors: no No. randomised: 286 No. analysed: 274 Intention‐to‐treat analysis: no Power and sample calculations described Duration of trial: from 1999 to 2001
Participants	Women undergoing oocyte aspiration Mean age: 33 years (range 22 to 38 years) Cause of infertility: male factor, tubal disease, endometriosis, PCOS, unexplained Similar demographic and infertility characteristics at baseline
Interventions	Control: conscious sedation and analgesia (IV alfentanil, dosage not stated) plus PCB (lidocaine, dosage not stated) (N = 145) Intervention: electro‐acupuncture (EA) plus PCB (lidocaine, dosage not stated) (N = 141) No premedication in either group
Outcomes	Primary: primary: intraoperative and postoperative pain (VAS 0 to 100) Secondary: ongoing pregnancy rate, pregnancy rate
Notes	Sweden Multi‐centre (5 IVF centres) Goteburg University Funding: Hjalmar Svensson's Foundation, the Wilhelm and Martina Lundgren's Foundation Twelve women (4%) dropped out (7 in control group, 5 in intervention group):  4 ‐ administration failure  1 ‐ fall in blood pressure  1 ‐ nausea  6 ‐ withdrew voluntarily Definition of pregnancy not documented
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Each centre used its own randomisation Method: random numbers table
Allocation concealment (selection bias)	Low risk	Adequate: sealed envelopes
Blinding (performance bias and detection bias)   All outcomes	Unclear risk	Blinding not possible owing to the nature of the interventions Blinding of assessors not reported
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	12 participants lost to follow‐up (4%)
Selective reporting (reporting bias)	Low risk	All prespecified outcomes reported
Other bias	Low risk	Comparable demographic and infertility characteristics at baseline

Study	Reason for exclusion
Atashkhoii 2006	Unable to obtain evidence of randomisation
Bovenschen 2002	Conscious sedation and analgesia not one of the comparators
Bumen 2010	Conscious sedation and analgesia not one of the comparators
Casati 1999	Conscious sedation and analgesia not one of the comparators
Corson 1994	Conscious sedation and analgesia not one of the comparators
Godoy 1993	Conscious sedation and analgesia not one of the comparators
Gotz 2014	Unable to obtain evidence of randomisation
Hadimioglu 2002	General anaesthesia. Conscious sedation not one of the comparators
Hong 2005	Conscious sedation and analgesia among low‐ and high‐anxiety patients. No comparison with another technique
Manica 1993	Spinal anaesthesia dose finding. Conscious sedation and analgesia not one of the comparators
Martin 1999	Spinal anaesthesia. Conscious sedation and analgesia not one of the comparators
Muir 1995	Subperitoneal xylocaine. Spinal anaesthesia dose finding. Conscious sedation and analgesia not one of the comparators
Ng 1999	Paracervical block with lignocaine vs normal saline vs no paracervical block. Conscious sedation and analgesia not one of the comparators
Ng 2000	Paracervical block dose finding. Conscious sedation and analgesia not one of the comparators
Ng 2002	Premedication versus no premedication. Conscious sedation and analgesia not one of the comparators
Ng 2003	Paracervical block dose finding. Conscious sedation and analgesia not one of the comparators
Oliveira 2016	Conscious sedation and analgesia not one of the comparators
Ongun 2002	Conscious sedation and analgesia not one of the comparators
Ramzy 2001	Conscious sedation and analgesia not one of the comparators
Saleh 2012	Conscious sedation and analgesia not one of the comparators
Sarikaya 2011	Population not clarified. No response from trial author when contacted
Singh 2014	Unable to obtain evidence of randomisation
Tsen 2001	Spinal anaesthesia. Conscious sedation not one of the comparators
Zaccabri 2001	Paracervical block vs vaginal anaesthetic cream. Conscious sedation and analgesia not one of the comparators
Zhang 2013	Conscious sedation and analgesia not one of the comparators

Methods	Randomisation: random numbers table used to divide into 2 groups Allocation concealment: not reported Blinding of participants/investigators: not reported Blinding of assessors: not reported No. randomised: 134 No. analysed: 134 Intention‐to‐treat analysis: yes Power and sample calculations: not described Duration of trial: not stated
Participants	Patients undergoing IVF‐E
Interventions	1. Control: intramuscular (IM) Dolantin 50 milligrams (mg) 30 minutes before oocyte retrieval (N = 67) 2. Intervention: IM Dolantin 50 mg 30 minutes before electro‐acupuncture (N = 67)
Outcomes	1. Primary: intraoperative pain (World Health Organization pain scale: Grade I (scores 1 to 3, minimal pain), Grade II (scores 4 to 6, mild pain), Grade III (scores 7 to 9, moderate pain), Grade IV (scores 10 to 12, severe pain)): postoperative (1 hour (h), 2 hours postoperatively) abdominal pain 2. Secondary: side effects of analgesia
Notes	China Reproductive Medicine Centre Funding: Gansu Province Paper in Chinese NB. Data unclear, awaiting response from trial authors

Trial name or title	A randomised controlled trial of oral acetaminophen for analgesic control after transvaginal oocyte retrieval
Methods	Double‐blind randomised controlled trial
Participants	Women undergoing IVF
Interventions	Transvaginal oocyte retrieval
Outcomes	Post‐procedure pain
Starting date	Not clear
Contact information	Email of co‐author: mpowell77@sky.com
Notes	Conference abstract published 2015. Trial authors/co‐authors contacted, no response