Abstract
Introduction
Study Design
Results
Conclusions
1. Introduction
- Kulier R
- Kapp N
- Gülmezoglu AM
- Hofmeyr GJ
- Cheng L
- Campana A.
Ministry of Health (Italy). Report Minister Health Implementation Law 194/78 maternity social protection and voluntary termination of pregnancy - definitive data 2017 [Relazione del ministro della salute sulla attuazione della legge contenente norme per la tutela sociale della maternita e per L'interruzione volontaria di gravidanza (Legge 194/78)]. 2018.
2. Materials and Methods
- Reynolds-Wright J
- Woldetsadik M
- Morroni C
- Cameron S.

3. Results
3.1 Study design and setting
3.2 Participants
3.3 Interventions
3.4 Outcomes
3.5 Excluded studies
- 91 did not include a pain relief intervention
- 23 had no English language full text available
- 16 were duplicates, not detected at initial upload of search
- 15 had a study design that did not meet inclusion criteria
- 9 used a comparator that did not meet inclusion criteria
- 6 had a patient population that did not meet inclusion criteria
- 2 had outcomes that did not meet the inclusion criteria
- 1 was a commentary article
3.6 Risk of bias in included studies
Study, outcome | Bias arising from the randomization process | Bias due to deviations from intended intervention | Bias due to missing outcome data | Bias in measurement of the outcome | Bias in selection of the reported result | Overall |
---|---|---|---|---|---|---|
Avraham 2012 Pain scores at two hours post-misoprostol administration | Low Quote: "The 61 women were randomized at the time of misoprostol administration into two treatment groups by providing a sealed envelope, using a computer-generated random list, with serial numbers from 1 to 61." | Low Quote: "The 61 women were randomized at the time of misoprostol administration into two treatment groups by providing a sealed envelope, using a computer-generated random list, with serial numbers from 1 to 61." | Low Quote: "Two women, one in each group, did not show up for follow-up, and data about the success of the abortion were not established. They were considered in our analysis as failure of the medical abortion." Comment: missing outcome data between the two groups were similar in proportion and the reason for missing were similar. | Low Quote: "this was a randomized, placebo-controlled, double-blind trial." Comment: Using ROB2 tool, assessed as 'Probably No' for this domain therefore LOW risk. | Low Comment: the study was analyzed and reported based on the authors plan | Low Comment: No other sources of bias were identified |
Friedlander 2018 Pain scores at multiple time points (immediately after misoprostol administration and then at 2, 6, 12, 24 and 72 hours later) | Low Quote: "A researcher not involved in the conduct of the study used a computer-generated randomization scheme of varied block sizes" | Low Quote: "A researcher not involved in the conduct of the study ... placed the allocated study capsule in sequentially numbered bags identified only by study identification number so as to maintain blinding of participants and researchers." | Low Comment: Using ROB2 tool: Domain 5.1 = Yes, 5.2 = No, 5.3 = No | Low Comment: Using ROB2 tool: Domain 4.1 =No, 4.2 = No, 4.3 = No Information, 4.4 = No | Low Comment: Study appears to have reported on all outcomes selected in analysis plan | Low Comment: No other specific concerns regarding sources of bias |
Livshits 2009 Pain scores at two hours post-misoprostol administration | Low Quote: "This was a prospective, double-blind, randomized controlled trial.... We randomized the 120 women into two treatment groups by providing a sealed envelope by using a computer-generated random list that included serial numbers from 1 to 120. The envelope was given by the nurse at the time at which the patient received the misoprostol tablets." | Low Quote: "This was a prospective, double-blind, randomized controlled trial....We randomized the 120 women into two treatment groups by providing a sealed envelope by using a computer-generated random list that included serial numbers from 1 to 120. The envelope was given by the nurse at the time at which the patient received the misoprostol tablets...The ibuprofen and paracetamol tablets were identical in size, color, and shape." | Low Quote: "We randomized the 120 women into two treatment groups by providing a sealed envelope by using a computer-generated random list that included serial numbers from 1 to 120. The envelope was given by the nurse at the time at which the patient received the misoprostol tablets...The ibuprofen and paracetamol tablets were identical in size, color, and shape." | Low Comment: Appears nurses were assessing outcomes and also blind to nature of trial medications | Low Comment: ROB2 Tool Domain 5.1 = Probably Yes, 5.2 = No, 5.3 = Probably No. The authors listed all analyses for table 2 but only show the ones that were significant, but can infer from text that remaining were not significant. | Low Comment: There did not appear to be any other significant sources of bias |
Raymond 2013 Worst pain in the 24-hour period following misoprostol | Low Quote: "The one-to-one randomization scheme was stratified by site and used randomly permuted blocks with sizes of eight and 20 generated by computer by the study statistician before the start of enrollment." | Low Quote: "If she was eligible, staff assigned her to either the prophylactic regimen group or the therapeutic regimen group by opening the next unused consecutively numbered opaque envelope containing a random assignment." | Low Comment: Missing data accounted for and any sections missing identified in results tables. All variables analysed as ordinal - nearly all data available. | High Comment: ROB2 tool questions 4.1 = No, 4.2 = No, 4.3 = Yes, 4.4 = Yes, 4.5 = Probably Yes. | Low Comment: ROB2 tool questions 5.1 = Probably Yes, 5.2 = Probably No, 5.3 = Probably No | Some concerns Comment: Recall scores of pain for those who did not complete diary will be affected by recall bias, however the number of participants doing this in both groups is small and so may not affect overall result, but cannot tell as results aggregated. |
Study | Bias due to confounding | Bias in selection of participants into the study | Bias in classification of interventions | Bias due to deviations from the intended intervention | Bias due to missing data | Bias in measurement of outcomes | Bias in selection of the reported result | Overall risk of bias |
---|---|---|---|---|---|---|---|---|
Ojha 2012 | Serious | Serious | Low | Low | Low | Low | Low | Serious |
Rationale for judgement | Comment: ROBINS-I tool questions 1.1 = Yes, 1.2 = Probably No, 1.4 = Probably No, 1.6 = Probably No, 1.7 = Probably No, therefore Judgement = serious risk of bias | Comment: Discussed within review team and felt that as participants could self-select intervention, at serious risk of bias. | Comment: ROBINS-I tool questions 3.1 = Yes, 3.2 = Yes, 3.3 = No, therefore Judgement = Low | Comment: ROBINS-I questions 4.1 = Probably No, 4.3 = Probably Yes, 4.4 = Probably Yes, 4.5 = Probably Yes, therefore Judgement = Low | Comment: ROBINS- I questions 5.1 = Yes, 5.2 = Probably No, 5.3 = Probably No, therefore Judgement = Low | Comment: Discussed within review team and felt that outcome measurements were unlikely to be significantly biased | Comment: ROBINS-I tool questions 7.1 = No, 7.2 = Probably No, 7.3 = Probably No, therefore Judgement = Low | Comment: More than one domain at serious risk of bias therefore study considered to be ‘serious’ risk of bias overall |
3.6.1 Randomized studies of an intervention
3.6.2 Non-randomised study of an intervention
3.7 Effects of interventions
3.7.1 Primary outcomes
Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
Risk with Paracetamol 2000 mg | Risk with Ibuprofen 1600 mg | |||||
Pain score | The mean pain score was 5.67 out of 10 | MD 2.26 out of 10 lower (3 lower to 1.52 lower) | - | 108 (1 RCT) | ⊕⊕⊕⊝ Moderate | |
Gastrointestinal side effects (nausea) - not reported | - | - | - | - | - | |
Gastroinestinal side effects (vomiting) - not reported | - | - | - | - | - | |
Gastrointestinal side effects (diarrhoea) - not reported | - | - | - | - | - | |
Complete abortion rate | 837 per 1000 | 915 per 1000 (766 to 973) | OR 2.11 (0.64 to 6.92) | 108 (1 RCT) | ⊕⊕⊝⊝ Low | |
Induction to expulsion interval - not reported | - | - | - | - | - | |
Unscheduled contact with care - not reported | - | - | - | - | - | |
Patient satisfaction with analgesia - not reported | - | - | - | - | - | |
Patient satisfaction with abortion care overall - not reported | - | - | - | - | - | |
Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
---|---|---|---|---|---|---|
Risk with placebo | Risk with pregabalin 300 mg | |||||
Pain score | The mean pain score was 5.5 out of 10 | MD 0.5 out of 10 lower (1.41 lower to 0.41 higher) | - | 107 (1 RCT) | ⊕⊕⊝⊝ Low | |
Gastrointestinal side effects (nausea) | 808 per 1000 | 781 per 1000 (581 to 902) | OR 0.85 (0.33 to 2.19) | 107 (1 RCT) | ⊕⊕⊝⊝ Low | |
Gastrointestinal side effects (vomiting) | 577 per 1000 | 509 per 1000 (323 to 690) | OR 0.76 (0.35 to 1.63) | 107 (1 RCT) | ⊕⊕⊝⊝ Low | |
Gastrointestinal side effects (diarrhoea) | 558 per 1000 | 508 per 1000 (324 to 689) | OR 0.82 (0.38 to 1.76) | 107 (1 RCT) | ⊕⊕⊝⊝ Low | |
Complete abortion rate - not reported | - | - | - | - | - | |
Induction to expulsion interval - not reported | - | - | - | - | - | |
Unscheduled contact with care - not reported | - | - | - | - | - | |
Patient satisfaction with analgesia | 686 per 1000 | 680 per 1000 (479 to 829) | OR 0.97 (0.42 to 2.21) | 104 (1 RCT) | ⊕⊕⊝⊝ Low | |
Patient satisfaction with abortion care overall | 608 per 1000 | 740 per 1000 (554 to 867) | OR 1.84 (0.80 to 4.22) | 105 (1 RCT) | ⊕⊕⊝⊝ Low |
Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
---|---|---|---|---|---|---|
Risk with Placebo | Risk with Ibuprofen 800 mg | |||||
Pain score | The mean pain score was 5.4 out of 10 | MD 1.4 out of 10 lower (3.33 lower to 0.53 higher) | - | 61 (1 RCT) | ⊕⊕⊝⊝ Low | |
Gastrointestinal side effects (nausea) | 594 per 1000 | 690 per 1000 (436 to 865) | OR 1.52 (0.53 to 4.37) | 61 (1 RCT) | ⊕⊕⊝⊝ Low | |
Gastrointestinal side effects (vomiting) | 281 per 1000 | 69 per 1000 (15 to 275) | OR 0.19 (0.04 to 0.97) | 61 (1 RCT) | ⊕⊕⊝⊝ Low | |
Gastrointestinal side effects (diarrhoea) - not reported | - | - | - | - | - | |
Complete abortion rate | 875 per 1000 | 828 per 1000 (543 to 952) | OR 0.69 (0.17 to 2.85) | 61 (1 RCT) | ⊕⊕⊝⊝ Low | |
Induction to expulsion interval - not reported | - | - | - | - | - | |
Unscheduled contact with care - not reported | - | - | - | - | - | |
Patient satisfaction with analgesia - not reported | - | - | - | - | - | |
Patient satisfaction with abortion care overall - not reported | - | - | - | - | - |
Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
---|---|---|---|---|---|---|
Risk with non-ambulation | Risk with ambulation | |||||
Pain score | The mean pain score was 2.4out of 5 | MD 0.1 out of 5 higher (0.26 lower to 0.46 higher) | - | 130 (1 observational study) | ⊕⊝⊝⊝ Very low, | |
Gastrointestinal side effects (nausea) - not reported | - | - | - | - | - | |
Gastrointestinal side effects (vomiting) - not reported | - | - | - | - | - | |
Gastrointestinal side effects (diarrhoea) - not reported | - | - | - | - | - | |
Complete abortion rate | Not pooled | Not pooled | Not pooled | (1 observational study) | ⊕⊝⊝⊝ Very low, | Complete abortion rate 100% in both study groups |
Induction to expulsion interval | The mean induction to expulsion interval was 233minutes | MD 2.3 minutes lower (38.78 lower to 34.18 higher) | - | 130 (1 observational study) | ⊕⊝⊝⊝ Very low, | |
Unscheduled contact with care - not reported | - | - | - | - | - | |
Patient satisfaction with analgesia - not reported | - | - | - | - | - | |
Patient satisfaction with abortion care overall - not reported | - | - | - | - | - |
Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
---|---|---|---|---|---|---|
Risk with prophylactic ibuprofen 800 mg | Risk with therapeutic ibuprofen 800 mg | |||||
Pain score | The mean pain score was 7.1 out of 10 | MD 0.2 out of 10 higher (0.41 lower to 0.81 higher) | - | 228 (1 RCT) | ⊕⊕⊝⊝ Low, | |
Gastrointestinal side effects (nausea and/or vomiting) | 378 per 1000 | 504 per 1000 (376 to 633) | OR 1.67 (0.99 to 2.83) | 228 (1 RCT) | ⊕⊕⊝⊝ Low, | |
Gastrointestinal side effects (diarrhoea) - not reported | - | - | - | - | - | |
Complete abortion rate | 964 per 1000 | 974 per 1000 (892 to 994) | OR 1.42 (0.31 to 6.50) | 228 (1 RCT) | ⊕⊕⊝⊝ Low, | |
Induction to expulsion interval - not reported | - | - | - | - | - | |
Unscheduled contact with care | 360 per 1000 | 367 per 1000 (253 to 499) | OR 1.03 (0.60 to 1.77) | 228 (1 RCT) | ⊕⊕⊝⊝ Low, | |
Patient satisfaction with analgesia - not reported | - | - | - | - | - | |
Patient satisfaction with abortion care overall | 982 per 1000 | 966 per 1000 (831 to 994) | OR 0.52 (0.09 to 2.89) | 228 (1 RCT) | ⊕⊕⊝⊝ Low, |
3.7.2 Secondary outcomes
4. Discussion
Acknowledgements
References
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Article info
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Footnotes
Funding: This study was conducted in part at the MRC Centre for Reproductive Health, Edinburgh, UK, which is supported by Medical Research Council (UK) grant MR/N022556/1This study was conducted in part at the MRC Centre for Reproductive Health, Edinburgh, UK, which is supported by Medical Research Council (UK) grant MR/N022556/1
Declaration of Competing Interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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