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Cochrane Database of Systematic Reviews Review - Intervention

Interventions to reduce haemorrhage during myomectomy for fibroids

Authors' declarations of interest

Version published: 15 August 2014 Version history

https://doi.org/10.1002/14651858.CD005355.pub5
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Abstract

available in

Background

Benign smooth muscle tumours of the uterus, known as fibroids or myomas, are often symptomless. However, about one‐third of women with fibroids will present with symptoms that are severe enough to warrant treatment. The standard treatment of symptomatic fibroids is hysterectomy (that is surgical removal of the uterus) for women who have completed childbearing, and myomectomy for women who desire future childbearing or simply want to preserve their uterus. Myomectomy, the surgical removal of myomas, can be associated with life‐threatening bleeding. Excessive bleeding can necessitate emergency blood transfusion. Knowledge of the effectiveness of the interventions to reduce bleeding during myomectomy is essential to enable evidence‐based clinical decisions. This is an update of the review published in The Cochrane Library (2011, Issue 11).

Objectives

To assess the effectiveness, safety, tolerability and costs of interventions to reduce blood loss during myomectomy.

Search methods

In June 2014, we conducted electronic searches in the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and PsycINFO, and trial registers for ongoing and registered trials.

Selection criteria

We selected randomised controlled trials (RCTs) that compared potential interventions to reduce blood loss during myomectomy to placebo or no treatment.

Data collection and analysis

The two authors independently selected RCTs for inclusion, assessed the risk of bias and extracted data from the included RCTs. The primary review outcomes were blood loss and need for blood transfusion. We expressed study results as mean differences (MD) for continuous data and odds ratios for dichotomous data, with 95% confidence intervals (CI). We assessed the quality of evidence using GRADE methods.

Main results

Eighteen RCTs with 1250 participants met our inclusion criteria. The studies were conducted in hospital settings in low, middle and high income countries.

Blood loss
We found significant reductions in blood loss with the following interventions:
vaginal misoprostol (2 RCTs, 89 women: MD ‐97.88 ml, 95% CI ‐125.52 to ‐70.24; I2 = 43%; moderate‐quality evidence); intramyometrial vasopressin (3 RCTs, 128 women: MD ‐245.87 ml, 95% CI ‐434.58 to ‐57.16; I2 = 98%; moderate‐quality evidence); intramyometrial bupivacaine plus epinephrine (1 RCT, 60 women: MD ‐68.60 ml, 95% CI ‐93.69 to ‐43.51; low‐quality evidence); intravenous tranexamic acid (1 RCT, 100 women: MD ‐243 ml, 95% CI ‐460.02 to ‐25.98; low‐quality evidence); gelatin‐thrombin matrix (1 RCT, 50 women: MD ‐545.00 ml, 95% CI ‐593.26 to ‐496.74; low‐quality evidence); intravenous ascorbic acid (1 RCT, 102 women: MD ‐411.46 ml, 95% CI ‐502.58 to ‐320.34; low‐quality evidence); vaginal dinoprostone (1 RCT, 108 women: MD ‐131.60 ml, 95% CI ‐253.42 to ‐9.78; low‐quality evidence); loop ligation of the myoma pseudocapsule (1 RCT, 70 women: MD ‐305.01 ml, 95% CI ‐354.83 to ‐255.19; low‐quality evidence); a fibrin sealant patch (1 RCT, 70 women: MD ‐26.50 ml, 95% CI ‐44.47 to ‐8.53; low‐quality evidence), a Foley catheter tied around the cervix (1 RCT, 93 women: MD ‐240.70 ml, 95% CI ‐359.61 to ‐121.79; low‐quality evidence), and a polyglactin suture round both cervix and infundibulopelvic ligament (1 RCT, 28 women: MD ‐1870.0 ml, 95% CI ‐2547.16 to 1192.84; low‐quality evidence). There was no good evidence of an effect on blood loss with oxytocin, morcellation or clipping of the uterine artery.

Need for blood transfusion
We found significant reductions in the need for blood transfusion with vasopressin (2 RCTs, 90 women: OR 0.15, 95% CI 0.03 to 0.74; I2 = 0%; moderate‐quality evidence); tourniquet tied round the cervix (1 RCT, 98 women: OR 0.22, 95% CI 0.09 to 0.55; low‐quality evidence); tourniquet tied round both cervix and infundibulopelvic ligament (1 RCT, 28 women: OR 0.02, 95% CI 0.00 to 0.23; low‐quality evidence); gelatin‐thrombin matrix (1 RCT, 100 women: OR 0.01, 95% CI 0.00 to 0.10; low‐quality evidence) and dinoprostone (1 RCT, 108 women: OR 0.17, 95% CI 0.04 to 0.81; low‐quality evidence), but no evidence of effect on the need for blood transfusion with misoprostol, oxytocin, tranexamic acid, ascorbic acid, loop ligation of the myoma pseudocapsule and a fibrin sealant patch.

There were insufficient data on the adverse effects and costs of the different interventions.

Authors' conclusions

At present there is moderate‐quality evidence that misoprostol or vasopressin may reduce bleeding during myomectomy, and low‐quality evidence that bupivacaine plus epinephrine, tranexamic acid, gelatin‐thrombin matrix, ascorbic acid, dinoprostone, loop ligation, a fibrin sealant patch, a peri‐cervical tourniquet or a tourniquet tied round both cervix and infundibulopelvic ligament may reduce bleeding during myomectomy. There is no evidence that oxytocin, morcellation and temporary clipping of the uterine artery reduce blood loss. Further well designed studies are required to establish the effectiveness, safety and costs of different interventions for reducing blood loss during myomectomy.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Plain language summary

available in

Interventions to reduce haemorrhage during myomectomy for treating fibroids

Background

Some women have non‐cancerous growths of the uterus, called fibroids. In a third of cases the fibroids produce symptoms, such as vaginal bleeding, that warrant treatment. The surgical removal of the fibroids, called myomectomy, is one of the treatment options for fibroids. It can be accomplished by either laparotomy (through an incision into the abdomen) or laparoscopy (keyhole surgery). The procedure is associated with heavy bleeding. Many interventions have been used by doctors to reduce bleeding during an operation for removing fibroids but it is unclear whether or not the interventions are effective.

Study characteristics

The evidence is current to June 2014. The review included 18 studies with a total of 1250 women who had myomectomy for uterine fibroids. All studies compared an intervention to reduce bleeding during myomectomy with either a placebo or no such treatment.

Key results

The data available suggest that vaginal insertion of misoprostol and infiltration of vasopressin into the uterine muscle are effective in reducing bleeding during myomectomy. Limited data available also suggest that chemical dissection (such as with mesna), vaginal insertion of dinoprostone, a gelatin‐thrombin matrix, tranexamic acid, infusion of vitamin C (ascorbic acid) during surgery, infiltration of a mixture of bupivacaine and epinephrine into the uterine muscles, the use of fibrin sealant patch (a surgical patch that improves blood clotting) or a tourniquet around the cervix or around both the cervix and the infundibulopelvic ligamentmay be effective in reducing bleeding during myomectomy. We found limited information on the harms (adverse effects) of the different interventions.

Quality of the evidence

There is moderate‐quality evidence that misoprostol reduces blood loss by between 70.24 ml and 125.52 ml; with a laparotomy vasopressin reduces blood loss by between 392.51 and 507.49 ml during myomectomy, and by between 121.73 ml and 172.17 ml during laparoscopic myomectomy. There is low‐quality evidence for the rest of the interventions (chemical dissection, dinoprostone, gelatin‐thrombin matrix, tranexamic acid, vitamin C, mixture of bupivacaine and epinephrine, a fibrin sealant patch and the two types of tourniquet).

Authors' conclusions

Implications for practice

Currently, there is moderate‐quality evidence that misoprostol (MD ‐97.88 ml, 95% CI ‐125.52 to ‐70.24) and vasopressin (MD ‐245.87 ml, 95% CI ‐434.58 to ‐57.16), and low‐quality evidence that bupivacaine plus epinephrine (MD ‐68.60 ml, 95% CI ‐93.69 to ‐43.51), gelatin‐thrombin matrix (MD ‐545.00 ml, 95% CI ‐593.26 to ‐496.74), tranexamic acid (MD ‐243 ml, 95% CI ‐460.02 to ‐25.98), peri‐cervical tourniquet (MD ‐240.70 ml. 95% CI ‐359.61 to 121.7),tourniquet round both the cervix and the infundibulopelvic ligament (MD 1870.00 ml, 95% CI ‐2547.16, to ‐1192.84), ascorbic acid (MD ‐411.46 ml, 95% CI ‐502.58 to ‐320.34), dinoprostone (MD ‐131.60 ml, 95% CI ‐253.42 to ‐9.78), loop ligation of the myoma pseudocapsule (MD ‐305.01 ml, 95% CI ‐354.83 to ‐255) and a fibrin sealant patch (MD ‐26.50, 95%CI ‐44.47 to ‐8.53) may reduce blood loss during myomectomy. However, since we did not include trials with head‐to‐head comparisons, we cannot draw any conclusions about the superiority of one intervention over the other. Due to the small reduction in blood loss (< 70 ml), the use of bupivacaine plus epinephrine and a fibrin sealant patch have limited clinical importance. At present there is no evidence that oxytocin, myoma enucleation by morcellation, and the temporary clipping of uterine arteries during myomectomy have an effect on intraoperative blood loss.

Implications for research

There is a need for well designed randomised controlled trials to shed more light on the effectiveness of different interventions in reducing blood loss during myomectomy. To date, a few randomised trials, often will small sample sizes, have addressed this issue and so there is a need to fill the current gap of knowledge which has very important practical implications. Apart from the effectiveness, data on the cost‐effectiveness, future pregnancy (if desired), and adverse effects of different interventions are lacking. This is important for clinical decision making since such decisions are based on trade offs between benefits on the one hand and costs and adverse events on the other.

Summary of findings

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Summary of findings for the main comparison. Interventions to reduce blood loss during myomectomy for fibroids compared to placebo or no treatment

Interventions to reduce blood loss during myomectomy for fibroids compared to placebo or no treatment

Population: Women with fibroids
Settings: Various settings in low income, middle income, and high income countries
Intervention: Diverse interventions
Comparison: Placebo or no treatment

Intervention

Illustrative comparative risks (95% CI) on blood loss

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Placebo or no treatment

Interventions

Misoprostol in abdominal myomectomy

Mean blood loss with placebo was
621 ml

Mean blood loss with misoprostol was
149.00 ml lower
(229.24 to 68.76 lower)

MD ‐149.00 (‐229.24 to ‐68.76)

25
(1 study)

⊕⊕⊕⊝
moderate

We rated down the quality of evidence (by 1) because the data were derived from one small study

Misoprostol in laparoscopic myomectomy

Mean blood loss with placebo was
322.39 ml

Mean blood loss with misoprostol was
91.00 ml lower
(120.44 to 61.56 lower)

MD ‐91.00 (‐120.44 to ‐61.56)

64
(1 study)

⊕⊕⊕⊝
moderate

We rated down the quality of evidence (by 1) because the data were derived from one small study

Vasopressin

Mean blood loss with placebo was
483.09 ml

Mean blood loss with vasopressin was
245.87 ml lower
(434.58 to 57.16 lower)

MD ‐245.87 (‐434.58 to ‐57.16)

128
(3 studies)

⊕⊕⊕⊝
moderate

We rated down the quality of evidence (by 1) because the data were derived from three small studies

Bupivicaine plus epinephrine

Mean blood loss with placebo was
212.5 ml

Mean blood loss with bupivicaine‐epinephrine was
68.6 ml lower
(93.69 to 43.51 lower)

MD ‐68.60 (‐93.69, ‐43.51)

60
(1 study)

⊕⊕⊝⊝
low

We rated down the quality of evidence (by 2) because the data were derived from one small study, with a high risk of attrition bias (2 patients in each arm did not receive assigned intervention because of concomitant disease)

Intravenous injection of tranexamic acid

Mean blood loss with placebo was
1047 ml

Mean blood loss with tranexamic was
243 ml lower
(460.02 to 25.98 lower)

MD ‐243.00 (‐460.02 to ‐25.980

100
(1 study)

⊕⊕⊝⊝
low

We rated down the quality of evidence (by 2) because the data were derived from one small study and the pooled effect estimate was imprecise

Gelatin‐thrombin matrix

Mean blood loss with placebo was
625 ml

Mean blood loss with Gelatin‐thrombin was
545 ml lower
(593.26 to 496.74 lower)

MD ‐545.00 (‐593.26 to ‐496.74)

50
(1 study)

⊕⊕⊝⊝
low

We rated down the quality of evidence (by 2) because the data were derived from one small study, and it is unclear if outcome assessors were blind

Ascorbic acid

Mean blood loss with no treatment was
932.9 ml

Mean blood loss with ascorbic acid was
411.46 ml lower
(502.58 to 320.34 lower)

MD ‐411.46

(‐502.58 to ‐320.34)

102
(1 study)

⊕⊕⊝⊝
low

We rated down the quality of evidence (by 2) because the data were derived from one small study, and it is unclear how allocation concealment was done

Dinoprostone (prostaglandin E2 analogue)

Mean blood loss with placebo was
485.7 ml

Mean blood loss with dinoprostone was
131.6 ml lower
(253.42 to 9.78 lower)

MD ‐131.60

(‐253.42 to ‐9.78)

108
(1 study)

⊕⊕⊝⊝
low

We rated down the quality of evidence (by 2) because the data were derived from one small study, and the effect estimate has wide confidence intervals

Loop ligation of myoma pseudocapsule plus vasopressin

Mean blood loss with no treatment was
363.68 ml

Mean blood loss with loop ligation was
305.01 lower
(354.83 to 255.19 lower)

MD ‐305.01

(‐354.83 to ‐255.19)

70
(1 study)

⊕⊕⊝⊝
low

We rated down the quality of evidence (by 2) because the data were derived from one small study, and it is unclear how allocation concealment was done

Fibrin sealant patch (collagen sponge with thrombin and fibrinogen)

Mean blood loss with no treatment was
151.1 ml

Mean blood loss with tachosil was
26.5 ml lower
(44.47 to 8.53 lower)

MD ‐26.50

(‐44.47 to ‐8.53)

70
(1 study)

⊕⊕⊝⊝
low

We rated down the quality of evidence (by 2) because the data were derived from one small study, and the effect estimate has wide confidence intervals

CI: Confidence interval; MD: mean difference

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

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Summary of findings 2. Misoprostol compared to placebo to reduce blood loss during myomectomy for fibroids

Misoprostol compared to placebo to reduce blood loss during myomectomy for fibroids

Patient or population: Women with fibroids
Settings: Middle and high income countries
Intervention: Misoprostol
Comparison: Placebo

Outcomes

Illustrative comparative risks (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Placebo

Misoprostol

Blood loss (ml)
Estimated blood loss during myomectomy

The mean blood loss in placebo group was
322.39 ml

The mean blood loss in misoprostol group was
97.88 ml lower
(125.52 to 70.24 lower)

MD ‐97.88 (‐125.52 to ‐70.24)

89
(2 studies)

⊕⊕⊕⊝
moderate1

We rated down the quality of evidence (by 1) because the data were derived from two small studies and we could not rule out the possibility of publication bias

Need for blood transfusion
Number of participants who received blood transfusion

87 per 1000

31 per 1000
(4 to 217)

OR 0.36
(0.05 to 2.5)

89
(2 studies)

⊕⊕⊝⊝
low1

We rated down the quality of evidence (by 2) because (i) we could not conclusively rule out the possibility of publication bias and (ii) the pooled effect had wide confidence intervals

Duration of surgery (min)
Operative time

The mean duration of surgery in placebo group was
69.57 min for abdominal myomectomy and 77 min for laparoscopic myomectomy

The mean duration of surgery in misoprostol group was
9.50 min lower
(15.90 lower to 3.10 lower) in abdominal myomectomy and 9 min higher (1.63 lower to 19.63 higher) in laparoscopic myomectomy

MD ‐9.50

(‐15.90 to ‐3.10) for abdominal myomectomy &

MD 9.00

(‐1.63 to 19.63) for laparoscopic myomectomy

25
(1 study) for abdominal myomectomy &

64

(1 study) for laparoscopic myomectomy

⊕⊕⊝⊝
low1

We rated down the quality of evidence (by 2) because (i) we could not conclusively rule out the possibility of publication bias and (ii) the pooled effect had wide confidence intervals

We did not rate down the evidence due to heterogeneity because this could be explained by the type of myomectomy (laparoscopy versus laparotomy)

CI: Confidence interval; MD: mean difference; OR: Odds ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1In one trial the method of allocation concealment was not reported and in the other trial, allocation concealment was achieved using sequentially numbered opaque sealed envelopes.

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Summary of findings 3. Vasopressin versus placebo to reduce blood loss during myomectomy for fibroids

Vasopressin versus placebo to reduce blood loss during myomectomy for fibroids

Patient or population: Women with fibroids
Settings: Middle and low income countries
Intervention: Vasopressin
Comparison: Placebo

Outcomes

Illustrative comparative risks (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Placebo

Vasopressin

Blood loss (ml)
Estimated blood loss during myomectomy

The mean blood loss in the placebo groups was
483.09 ml

The mean blood loss in the vasopressin groups was
245.87 ml lower
(434.58 to 57.16 lower)

MD ‐245.87 (‐434.58 to ‐57.16)

128
(3 studies)

⊕⊕⊕⊝
moderate1

We rated down the quality of evidence (by 1) because the data were derived from three small studies and we could not rule out the possibility of publication bias

We did not rate down the evidence due to heterogeneity because this could be explained by the fact that in one study women had laparoscopic myomectomy and two other studies, women has open abdominal myomectomy

Need for blood transfusion
Participants who received blood transfusion

222 per 1000

33 per 1000
(7 to 164)

OR 0.15
(0.03 to 0.74)

90
(2 studies)

⊕⊕⊕⊝
moderate1

We rated down the quality of evidence (by 1) because the data were derived from two small studies and we could not rule out the possibility of publication bias

Duration of surgery
Operative time

The mean duration of surgery in the placebo groups was
111.45 min

The mean duration of surgery in the vasopressin groups was
27.72 min lower
(35.82 to 19.61 lower)

MD ‐27.72 (‐35.82 to ‐19.61)

108
(2 studies)

⊕⊕⊕⊝
moderate1

We rated down the quality of evidence (by 1) because the data were derived from two small studies and we could not rule out the possibility of publication bias

CI: Confidence interval; MD: mean difference; OR: Odds ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1In all the trials, allocation concealment was unclear.

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Summary of findings 4. Bupivicaine plus epinephrine compared to placebo to reduce blood loss during myomectomy for fibroids

Bupivicaine plus epinephrine compared to placebo to reduce blood loss during myomectomy for fibroids

Patient or population: Women with fibroids
Settings: University hospital in Italy
Intervention: Bupivicaine plus epinephrine
Comparison: Placebo

Outcomes

Illustrative comparative risks (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Placebo

Bupivicaine plus epinephrine

Blood loss (ml)
Estimated blood loss during myomectomy

The mean blood loss in the placebo group was
212.5 ml

The mean blood loss in the bupivicaine‐epinephrine group was
68.6 ml lower
(93.69 to 43.51 lower)

MD ‐68.60 (‐93.69 to ‐43.51)

60
(1 study)

⊕⊕⊝⊝
low1

We rated down the quality of evidence (by 2) because the data were derived from one small study, with a high risk of attrition bias (2 patients in each arm did not receive assigned intervention because of concomitant disease)

Need for blood transfusion

Participants who received blood transfusion

Outcome not reported by investigators

Duration of surgery (min)
Operative time

The mean duration of surgery in the placebo group was
109.2 min

The mean duration of surgery in the bupivicaine‐epinephrine group was
30.50 min lower
(37.68 to 23.32 lower)

MD ‐30.50 (‐37.68 to ‐23.32)

60
(1 study)

⊕⊕⊝⊝
low1

We rated down the quality of evidence (by 2) because the data were derived from one small study, with a high risk of attrition bias (2 patients in each arm did not receive assigned intervention because of concomitant disease)

CI: Confidence interval; MD: mean difference

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1The allocation concealment was achieved by envelopes containing computer‐generated random numbers.

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Summary of findings 5. Peri‐cervical tourniquet compared to no treatment to reduce blood loss during myomectomy for fibroids

Peri‐cervical tourniquet compared to no treatment to reduce blood loss during myomectomy for fibroids

Patient or population: Women with fibroids
Settings: Low and high income countries
Intervention: Tourniquet around the cervix only, or around both the cervix and the infundibulopelvic ligament
Comparison: No treatment

Outcomes

Illustrative comparative risks (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

No treatment

Peri‐cervical tourniquet

Blood loss (ml)
Estimated blood loss during myomectomy

The mean blood loss in the control groups was
756.4 ml (for cervical tourniquet) &2359.0 ml (for cervical plus infundibulopelvic ligament tourniquet)

The mean blood loss in the intervention groups was
240.70 ml lower
(359.61 ml lower to 121.79 ml lower) for the cervical tourniquet study & 1870 ml lower (2547.16 ml lower to 1192.84 ml lower) for the cervical plus infundibulopelvic ligament tourniquet study

MD ‐240.70 (‐359.61 to ‐121.79) for cervical touniquet study & ‐1870 (‐2547.16 to ‐1192.84) for the cervical plus infundibulopelvic ligament tourniquet study

121
(2 studies)

⊕⊕⊝⊝
low1

We rated down the quality of evidence (by 2) because the data were derived from two small studies that were not pooled together due to significant clinical and statistical heterogeneity.

One study used polyglactin suture round both the cervix and infundibulopelvic ligament, while the other used a Foley catheter round the cervix.

Need for blood transfusion
Participants who received blood transfusion

539 per 1000 for cervical tourniquet study &786 per 1000 for cervical plus infundibulopelvic ligament study

204 per 1000
for cervical tourniquet study &71 per 1000 for cervical plus infundibulopelvic ligament study

OR 0.22
(0.09 to 0.55) or cervical tourniquet study &

OR 0.02

(0.00 to 0.23) for cervical plus infundibulopelvic ligament study

121
(2 studies)

⊕⊕⊝⊝
low1

We rated down the quality of evidence (by 2) because the data were derived from two small studies which were not pooled together because of significant heterogeneity.

One study used polyglactin suture round both the cervix and infundibulopelvic ligament, while the other used a Foley catheter round the cervix.

Duration of surgery (min)
Operative time

The mean duration of surgery in the control groups was
118 min

The mean duration of surgery in the intervention groups was
4 min lower
(29.28 lower to 21.28 higher)

MD ‐4.00

(‐29.28 to 21.28)

28
(1 study)

⊕⊝⊝⊝
very low

We rated down the quality of evidence (by 3) because the data were derived from one small study and the effect estimate was imprecise

CI: Confidence interval; MD: mean difference; OR: Odds ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1In one trial the allocation concealment was unclear and in the other trial allocation concealment was achieved by sealed sequentially‐numbered opaque envelopes containing computer‐generated random numbers.

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Summary of findings 6. Gelatin‐thrombin matrix compared to placebo or no treatment to reduce blood loss during myomectomy for fibroids

Gelatin‐thrombin matrix compared to placebo or no treatment to reduce blood loss during myomectomy for fibroids

Patient or population: Women with fibroids
Settings: University teaching hospital in Spain
Intervention: Gelatin‐thrombin matrix
Comparison: Placebo or no treatment

Outcomes

Illustrative comparative risks (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Placebo

Gelatin‐thrombin matrix

Blood loss (ml)
Estimated blood loss during myomectomy

The mean blood loss in placebo groups was
625 ml

The mean blood loss in intervention groups was
545 ml lower
(593.26 to 496.74 lower)

MD ‐545.00 (‐593.26 to ‐496.74)

50
(1 study)

⊕⊕⊝⊝
low1

We rated down the quality of evidence (by 2) because the data were derived from one small study, and it is unclear if outcome assessors were blind

Need for blood transfusion
Participants who received blood transfusion

400 per 1000

4 per 1000
(0 to 40)

OR 0.01
(0 to 0.1)

50
(1 study)

⊕⊕⊝⊝
low1

We rated down the quality of evidence (by 2) because the data were derived from one small study, it is unclear if outcome assessors were blind, and the effect estimate was imprecise

Duration of surgery (min)
Operative time

The mean duration of surgery in placebo group was
60 min

The mean duration of surgery in intervention group was
5.00 min higher
(1.29 to 8.71 higher)

MD 5.00

(1.29 to 8.71)

50
(1 study)

⊕⊕⊝⊝
low1

We rated down the quality of evidence (by 2) because the data were derived from one small study, it is unclear if outcome assessors were blind, and the effect estimate was imprecise

CI: Confidence interval;MD: Mean difference; OR: Odds ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Allocation concealment not reported.

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Summary of findings 7. Ascorbic acid compared to no treatment to reduce blood loss during myomectomy for fibroids

Ascorbic acid compared to placebo or no treatment to reduce blood loss during myomectomy for fibroids

Patient or population: Women with fibroids
Settings: Tertiary hospital in Iran
Intervention: Ascorbic acid
Comparison: No treatment

Outcomes

Illustrative comparative risks (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

No treatment

Ascorbic acid

Blood loss (ml)
Estimated blood loss during myomectomy

The mean blood loss in the control group was
932.9 ml

The mean blood loss in the intervention group was
411.46 ml lower
(502.58 to 320.34 lower)

MD ‐411.46

(‐502.58 to ‐320.34)

102
(1 study)

⊕⊕⊝⊝
low1

We rated down the quality of evidence (by 2) because the data were derived from one small study, and it is unclear how allocation concealment was done

Need for blood transfusion
Participants who received blood transfusion

180 per 1000

68 per 1000
(20 to 238)

OR 0.38
(0.11 to 1.32)

104
(1 study)

⊕⊝⊝⊝
very low1

We rated down the quality of evidence (by 2) because the data were derived from one small study, it is unclear how allocation concealment was done, and the estimate was imprecise

Duration of surgery (min)
Operative time

The mean duration of surgery in the control group was
68 min

The mean duration of surgery in the intervention group was
26.00 min lower
(33.1 to 18.9 lower)

MD ‐26.00

(‐33.10 to ‐18.90)

102
(1 study)

⊕⊕⊝⊝
low1

We rated down the quality of evidence (by 2) because the data were derived from one small study, and it is unclear how allocation concealment was done

CI: Confidence interval; MD: Mean difference; OR: Odds ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Allocation concealment not reported.

Background

Description of the condition

Uterine leiomyomas (fibroids or myomas) are benign, smooth muscle tumours of the human uterus. Most myomas are asymptomatic (symptomless) and are discovered incidentally during a routine pelvic examination or imaging studies (Vollenhoven 1990). However, about 20% to 50% of women with myomas will present with symptoms severe enough to warrant treatment (Vercellini 1993). Myomas are three times more prevalent in black women, who tend to have larger, more numerous myomas, than their white counterparts (Jacoby 2010).

The standard treatment of symptomatic leiomyomas is hysterectomy for women who have completed childbearing, and myomectomy for women who wish to preserve fertility. Hysterectomy, the surgical removal of the uterus, eliminates both the symptoms and the chance of recurrence. However, many women who suffer from myomas desire future childbearing or want to preserve their uterus. For these women myomectomy, the surgical removal of the myomas with reconstruction and preservation of the uterus, is an important option. Myomectomy can be accomplished by laparotomy, laparoscopy or hysteroscopy. Myomectomy by laparotomy involves the surgical removal of the fibroids through an incision in the abdominal wall. Where there are a small number of subserous or intramural myomas and the uterine size is less than that of 16 weeks gestation, laparoscopic myomectomy may be an option (Hurst 2005). The laparoscopic approach is a minimal access technique (keyhole surgery) developed to minimize insult to the abdominal wall and to ensure quick recovery of the patient following surgery (Hasson 1992). For women with submucous myomas, transcervical hysteroscopic resection is a good option both for the gynaecologic surgeons (Derman 1991) and their patients.

Myomectomy can lead to both short and long‐term complications. Complications of hysteroscopic myomectomy include haemorrhage, uterine perforation, cervical damage and metabolic disturbances from excessive absorption of the distension medium, such as glycine (Cooper 2000). Laparoscopic myomectomy is associated with the usual risks of laparoscopy, particularly accidents during trocar (a surgical instrument) placement; and, additionally, excessive uncontrolled haemorrhage with the need to convert to a laparotomy and the risk of uterine rupture in subsequent pregnancies (Dubuisson 1997). Short‐term complications of abdominal myomectomy include bleeding, fever, infection, visceral damage and thromboembolism (LaMote 1993). A requirement for transfusion in up to 20% of cases following abdominal myomectomy has been reported in the literature (LaMote 1993). Patients undergoing myomectomy have an unusually high incidence of fever occurring in the first 48 hours following surgery (Iverson 1999). The incidence of postoperative fever following myomectomy has been reported to be as high as 36% (Celik 2003). The cause is unknown but it is believed that 'myomectomy fever' is due to the release of pyrogenic (fever‐inducing) factors during myoma dissection or to haematomas (blood clots) forming in defects left by the removed myomas. In 2% of cases there is a need for conversion of myomectomy to hysterectomy (Aubuchon 2002). Long‐term complications of abdominal myomectomy include pelvic adhesions in 59% of women after two years (Frederick 2002) and recurrent fibroids in 46.0% of women after one year (Nishiyama 2006). The risk of uterine rupture in subsequent pregnancies varies between 0% and 1% (Garnet 1964; Tulandi 1993; Fedele 1995; Somigliana 2008).

Blood loss during myomectomy can be intraoperative or postoperative and with haematoma formation. Massive blood loss associated with the dissection of huge fibroids renders myomectomy a more technically challenging procedure than hysterectomy. Sometimes myomectomy is converted to hysterectomy intraoperatively when bleeding becomes heavy and uncontrollable or when it is impossible to reconstruct the uterus because of the many defects left by the removal of multiple myomas (Iverson 1996). Excessive bleeding can necessitate emergency blood transfusion.

Description of the intervention

Many interventions have been performed to reduce bleeding during myomectomy. Four categories of interventions can be identified:

  • interventions on uterine arteries such as laparoscopic uterine artery dissection, uterine artery embolization, peri‐cervical mechanical tourniquet, vasopressin (natural or synthetic), a vasoconstrictive solution of bupivacaine plus epinephrine, and temporary clipping of the uterine artery;

  • utero‐tonics such as ergometrine, oxytocin, misoprostol, and sulprostone;

  • myoma dissection techniques which include myoma enucleation by morcellation and the use of laser and chemical dissectors such as sodium‐2‐mercaptoethane sulphonate (mesna);

  • pharmacologic manipulation of the coagulation cascade with antifibrinolytic agents such as tranexamic acid, aprotinin, aminocaproic acid, recombinant factor VIIa (Koh 2003), and gelatin‐thrombin haemostatic sealant.

In developed countries, gonadotrophin‐releasing hormone (GnRH) analogues (GnRHa) have been used prior to myomectomy. There is now clear evidence that the use of GnRH analogues reduces uterine volume and fibroid size and may reduce blood loss and operating time during myomectomy (Lethaby 2001). Although the use of preoperative GnRHa leads to less frequent vertical incisions in the case of myomectomy, a review of the cost‐effectiveness of GnRHa found that the costs outweigh its benefits (Farquhar 2002). In addition, uterine artery embolization (UAE) has been used as an alternative to myomectomy (Lumsden 2002) and to prevent haemorrhage during myomectomy (Ngeh 2004). However, there are currently no randomised trials comparing UAE with a placebo or no treatment with regard to blood loss during myomectomy. In low and middle income countries, however, the cost of using GnRH analogues and UAE may be prohibitive (especially where there is an out‐of‐pocket payment) and the necessary technology may not be available.

How the intervention might work

The mechanical tourniquet has been used during myomectomy to reduce intraoperative blood loss (Hutchins 1996). However, the pressure exerted by the tourniquet may cause damage to the uterine artery and its branches, and mask inadequate haemostasis (arrest of bleeding), which only becomes apparent once the tourniquet is removed. Uterine artery ligation can reduce both intraoperative and postoperative haemorrhage (Sapmaz 2003B). Hormonal tourniquets such as natural or synthetic vasopressin act on vasopressin V1a receptors, ubiquitously expressed in the myometrium, to reduce blood loss (Fletcher 1996; Dimitrov 1999; Kimura 2002). Hormonal tourniquets act as peri‐cervical tourniquets when administered in the cervix but act as utero‐tonics when administered in the myometrium. Preoperative UEA is a technique for the treatment of myomas which reduces uterine size and controls symptoms (Ravina 1995). It may also be a useful adjunct to surgery in women with massive fibroids (Ngeh 2004). Laparoscopic dissection of uterine vessels (LDUV) using ultrasonically activated shears for the treatment of fibroids has been reported to reduce uterine volume and symptoms (Holub 2003). Laparoscopic bipolar coagulation of the uterine blood vessels has recently been described as an alternative to UAE but a high degree of laparoscopic skill is required to isolate the uterine artery without causing damage to the ureters or blood vessels (Liu 2001).

Utero‐tonics such as ergometrine, oxytocin, misoprostol and sulprostone cause myometrial contraction and, therefore, potentially reduce blood loss during myomectomy leading to better anatomical reconstruction of the uterus (Baldoni 1995). Ergometrine may raise blood pressure while misoprostol may cause fever after its administration.

Myoma dissection techniques include the use of carbon dioxide laser and mesna for chemical dissection (McLaughin 1985). These procedures have the potential to minimize uterine defects from fibroid removal thereby facilitating uterine reconstruction, although they may be time consuming.

The coagulation cascade can be modified with the use of pharmacologic agents such as tranexamic acid, aprotinin, aminocaproic acid, recombinant factor VIIa and gelatin‐thrombin haemostatic sealant. These agents interfere with one or more stages of the coagulation cascade, from activation of coagulation to stabilisation of the fibrin clot. The end result is the formation of a stable clot that stops or prevents bleeding.

Why it is important to do this review

Excessive haemorrhage during myomectomy remains a major challenge to gynaecologic surgeons despite the many procedures that have been described to reduce intraoperative blood loss. The effects of these procedures on blood loss during myomectomy, as reported by previous non‐randomised studies, have been inconsistent. Moreover, the types of interventions are so varied that there is a need to identify the most effective procedures with minimal adverse effects to help the gynaecologic surgeon to make a correct choice.

The aim of this review was to establish which are the most effective interventions with the fewest adverse effects. The use of preoperative GnRHa was not considered in this review because their effectiveness has been examined in a separate Cochrane review (Lethaby 2001).

Objectives

To assess the effectiveness, safety, tolerability and costs of interventions to reduce blood loss during myomectomy.

Methods

Criteria for considering studies for this review

Types of studies

Published and unpublished randomised controlled trials (RCTs) were eligible for inclusion. We excluded non‐randomised studies (for example studies with evidence of inadequate sequence generation, such as patient numbers and alternate days) as they are associated with a high risk of bias.

Types of participants

Premenopausal women undergoing myomectomy (laparotomy, laparoscopy or hysteroscopy) for uterine fibroids, for any reason, were eligible for inclusion. Women who had previously had a myomectomy were also included.

Types of interventions

Trials comparing any intervention used to reduce blood loss during myomectomy versus either placebo or no treatment were eligible for inclusion. Only interventions performed during surgery, immediately before surgery, or within the 24 hour period prior to surgery were considered for this review. Interventions that involved GnRHa were excluded because their effectiveness has been examined in a separate Cochrane review (Lethaby 2001). The interventions, compared to placebo or no treatment, that were considered in this review were:

  • utero‐tonics (such as ergometrine, oxytocin, misoprostol, and sulprostone);

  • vasopressin (natural or synthetic);

  • uterine artery dissection and ligation;

  • peri‐cervical mechanical tourniquet;

  • uterine artery embolization (UAE);

  • laser dissection;

  • myoma enucleation by morcellation;

  • chemical dissection (such as sodium‐2‐mercaptoethane sulphonate (mesna));

  • antifibrinolytic agents (such as tranexamic acid);

  • temporary clipping of the uterine artery;

  • use of a gelatin‐thrombin haemostatic sealant.

Types of outcome measures

Trials with at least one of the following outcomes were eligible for inclusion.

Primary outcomes

  • Estimated blood loss in millilitres (ml)

  • Need for blood transfusion (as defined by trial authors)

Secondary outcomes

1. Effectiveness outcomes:

a) postoperative haemoglobin and haematocrit;

b) postoperative recurrence of myomas;

c) pregnancy (if pregnancy desired).

2. Safety outcomes:

a) duration of operation;
b) intraoperative hysterectomy;
c) conversion from laparoscopy to laparotomy;
d) other intraoperative complications (e.g. perforation, cervical damage);
e) duration of hospital stay in days;
f) postoperative morbidity (i.e. complications such as pyrexia, infection, thromboembolism, haematoma formation, and postoperative adhesions) as defined by the trial authors;
g) abdominal revisions for haemoperitoneum or pelvic haematoma;
h) treatment adherence (i.e. the proportion of patients who continued with the allocated treatment);
i) tolerability to the intervention, as defined by trial authors.

3. Cost outcomes:

a) cost of intervention;
b) total cost.

Search methods for identification of studies

We searched for all published and unpublished RCTs of myomectomy, without language restrictions and in consultation with the Menstrual Disorders and Subfertility Group (MDSG) Trials Search Co‐ordinator.

Electronic searches

The original searches were performed in March 2006 and subsequent searches were in September 2008, February 2011, October 2013 and 17 June 2014. In June 2014, we searched the following databases, trial registers and websites.

(1) The Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and PsycINFO.

(2) Other electronic sources of trials included the following.

  • Trial registers for ongoing and registered trials:

    • http://www.clinicaltrials.gov (a service of the US National Institutes of Health);

    • http://www.who.int/trialssearch/Default.aspx (World Health Organization International Clinical Trials Registry Platform search portal).

  • PubMed (for recent trials not yet indexed in MEDLINE).

  • DARE (Database of Abstracts of Reviews of Effects) in The Cochrane Library at http://onlinelibrary.wiley.com/o/cochrane/cochrane_cldare_articles_fs.html (for reference lists from relevant non‐Cochrane reviews).

Searching other resources

We handsearched reference lists of identified trials and relevant review articles, specialist journals, conference abstracts. In addition, we contacted experts in the field to obtain additional data.

Data collection and analysis

Selection of studies

The Trials Search Co‐ordinator of the Cochrane Menstrual Disorders and Subfertility Group and the lead author (EJK) conducted the literature search. After an initial screen of the titles and abstracts retrieved by the search, conducted by EJK, the full texts of all potentially eligible studies were retrieved. Both authors (EJK and CSW) independently examined these full text articles for compliance with the inclusion criteria and selected studies eligible for inclusion in the review. We also contacted the study investigators, as required, to clarify study eligibility. Any disagreements as to the study eligibility were resolved by discussion and consensus. The selection process was documented in a PRISMA flow chart.

Data extraction and management

The two authors (one a topic area specialist and one a methodologist) independently extracted the data from the eligible trials using a data extraction form designed and pilot‐tested by the authors. We then compared the results and any disagreements were resolved by discussion. The following information was extracted from each of the included studies.

Characteristics of trials:

  • power calculation;

  • method of randomisation;

  • blinding of patients, caregivers, outcome assessors, and investigators to treatment allocation;

  • quality of allocation concealment;

  • number of patients randomised, excluded, and lost to follow up;

  • handling in the analysis of losses to follow up and lack of compliance with the intervention;

  • duration, timing, and location of the study.

Characteristics of the study participants:

  • age, ethnic background, and any recorded characteristics of the study participants such as size of fibroids and reason for myomectomy;

  • other inclusion criteria;

  • exclusion criteria.

Interventions:

  • types of interventions;

  • dose, timing, duration, and route of administration of the treatment;

  • technique of myomectomy (abdominal, laparoscopic, or hysteroscopic).

Outcomes:

  • types of outcomes measured or reported;

  • methods used to assess outcome measures.

Where studies had multiple publications, the main trial report was used as the reference and additional details were derived from secondary articles. We contacted the study investigators for further data on methods and results, as required.

Assessment of risk of bias in included studies

The two authors independently assessed the risk of bias in the included trials by addressing the seven specific domains of the Cochrane risk of bias assessment tool (www.cochrane‐handbook.org): selection (random sequence generation and allocation concealment); performance (blinding of participants and personnel); detection (blinding of outcome assessors); attrition (incomplete outcome data); reporting (selective outcome reporting); and other bias, as outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). For risk of bias assessment we were not blinded to the names of the trial investigators, their institutions, journals of publication, nor results of the study. For each included trial we described all judgments fully and presented the conclusions in the risk of bias tables. The risk of bias was incorporated into the interpretation of the review findings by means of a sensitivity analysis. We searched for within‐trial selective reporting, such as trials failing to report obvious outcomes or reporting them in insufficient detail to allow for inclusion.

Measures of treatment effect

We performed statistical analysis using RevMan 5.2. For dichotomous data, we used numbers of events in the control and intervention groups of each study to calculate the Mantel‐Haenzel odds ratios (OR) with 95% confidence intervals (CI). For continuous data, if all studies reported exactly the same outcomes we calculated the mean difference (MD) between the groups. If they reported similar outcomes, we recorded the means and their standard deviations for each arm of the trial and expressed study results as mean difference (MD) with a 95% CI. We would have used standardised mean difference (SMD) if similar outcomes were reported on different scales across studies. If data to calculate the ORs and MDs were not available, we would have used the most detailed numerical data available that might have facilitated similar analyses of included studies (for example P values). We compared the magnitude and direction of effect reported by the studies with how they were presented in the review, taking account of legitimate differences.

Unit of analysis issues

The primary analysis was performed per woman randomised. We planned to check for 'unit‐of‐analysis error' in cluster‐randomised controlled trials. Unit‐of‐analysis error occurs if individuals in a cluster‐randomised trial are assumed to be independent and clustering is ignored during the analysis. We planned to handle these issues according to the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Dealing with missing data

Data were analysed on an intention‐to‐treat basis as far as possible. Where data were missing we contacted the study investigators and requested the missing data. Where only the median was reported we assumed that the mean was equal to the median and imputed the standard deviation from trials with similar values and sample sizes. Where similar trials were not available, we discussed the results of the study in a narrative format. If studies reported sufficient detail to calculate the mean differences but had no information on the associated standard deviation (SD), the outcome was assumed to have a SD equal to the highest SD from other studies within the same analysis.

Assessment of heterogeneity

We considered whether the clinical and methodological characteristics of the included trials were sufficiently similar for meta‐analysis to provide a clinically meaningful summary. We assessed statistical heterogeneity by the I2 statistic. An I2 value greater than 50% was taken to indicate substantial heterogeneity (Higgins 2011).

Assessment of reporting biases

We planned to assess publication bias by looking for funnel plot asymmetry if there were 10 or more studies in an analysis. In view of the difficulty of detecting and correcting for publication bias and other reporting biases, attempts were made to reduce reporting bias by searching multiple sources of electronic databases and additional sources for both published and unpublished articles.

Data synthesis

If the studies were sufficiently similar, we carried out a meta‐analysis of results from trials using the fixed‐effect model (DeMets 1987). However, when significant heterogeneity was found we reported the results of the random‐effects model (DerSimonian 1986) and explored potential sources of heterogeneity. We analysed trial participants in the groups to which they were randomised, regardless of whether they actually received the assigned treatment.

Higher values of postoperative haemoglobin and haematocrit, pregnancy after myomectomy, and treatment adherence were considered a benefit rather than adverse consequences of treatment, so the presence of the effect estimates (MD, OR) and CIs to the right side of the forest plots (rather than to the left as with blood loss and other outcomes) was considered to show a benefit of treatment.

Subgroup analysis and investigation of heterogeneity

We planned to perform subgroup analyses based on the technique of myomectomy (laparotomy, laparoscopy, or hysteroscopy), and type of comparison group (placebo or no treatment).

Sensitivity analysis

We planned to perform a sensitivity analysis by considering whether the review conclusions would have differed if:

  1. studies with high risk of bias had been excluded;

  2. a random‐effects model had been adopted;

  3. the summary effect measure was risk ratio rather than odds ratio (OR);

  4. we excluded studies with imputed data.

Overall quality of the body of evidence: summary of findings table

We generated summary of findings tables using the GRADEPRO software. These tables present the overall quality of the body of evidence for main review outcomes (that is blood loss, need for blood transfusion, and duration of surgery) taking into consideration study limitations (that is risk of bias), consistency of effect, imprecision, indirectness, and publication bias. Judgments about evidence quality (high, moderate or low) was justified, documented, and incorporated into reporting of results for each outcome (summary of findings Table for the main comparison; summary of findings Table 2; summary of findings Table 3; summary of findings Table 4; summary of findings Table 5; summary of findings Table 6; summary of findings Table 7).

Results

Description of studies

Results of the search

The search retrieved 623 records. Forty‐one studies were potentially eligible and were retrieved in full text. Eighteen studies met our inclusion criteria. Twenty‐three studies were excluded and two are ongoing.

The October 2013 search identified six additional trials (Kalogiannidis 2011; Leone Maggiore 2011; Zhao 2011; Pourmatroud 2012; Vercellino 2012; Shokeir 2013) to the 12 trials that were included in the previous version of the review (Kongnyuy 2011). See study tables: Characteristics of included studies; Characteristics of excluded studies; and Characteristics of ongoing studies. The search and selection processes for the review are shown in Figure 1.

Figure 1
Flow diagram showing screening of search outputs and study selection.

Flow diagram showing screening of search outputs and study selection.

Included studies

Study design and setting

Eighteen parallel‐design randomised controlled trials (RCTs) were included in the review. The studies were conducted in hospital settings in low, middle and high income countries. All studies were carried out in one centre except for two studies (Taylor 2005; Vercellino 2012) that were conducted in two or more centres.

Participants

The studies included 633 women in the intervention groups and 617 in the control groups. All were women of reproductive age with uterine myomas and wished to preserve their uteri. Most women had symptomatic fibroids. One trial included only infertile women (Assaf 1999). There were no significant differences between the treatment and control groups at baseline in all trials but one (Taylor 2005), in which there was a significant difference in the mean age: 39.5 years in the control group and 42.6 years in the treatment group.

Interventions

  • 3/18 studies compared vasopressin versus placebo

  • 1/18 studies compared bupivacaine combined with epinephrine versus placebo

  • 1/18 studies compared peri‐cervical tourniquet versus no treatment

  • 1/18 studies compared a tourniquet round both cervix and infundibulopelvic ligament versus no treatment

  • 2/18 studies compared oxytocin versus placebo

  • 2/18 studies compared misoprostol versus placebo

  • 1/18 studies compared chemical dissection with mesna versus placebo

  • 1/18 studies compared morcellation while attached to the uterus versus no treatment

  • 1/18 studies compared gelatin‐thrombin matrix versus placebo

  • 1/18 studies compared ascorbic acid versus no treatment

  • 1/18 studies compared dinoprostone versus placebo

  • 1/18 studies compared loop ligation of myoma pseudocapsule combined with vasopressin versus no treatment

  • 1/18 studies compared temporary clipping of uterine artery versus no treatment

  • 1/18 studies compared fibrin sealant patch (surgical collagen patch coated with thrombin and fibrinogen) versus no treatment

Eight of the trials included in this review used laparoscopic myomectomy (Assaf 1999; Zullo 2004; Sinha 2005; Wang 2007; Kalogiannidis 2011; Leone Maggiore 2011; Zhao 2011; Vercellino 2012), one trial included cases that had myomectomy by either the vaginal route or laparotomy (Agostini 2005) and the rest of the trials used myomectomy by laparotomy only.

Outcomes

  • 16/18 studies reported blood loss (ml) during myomectomy

  • 13/18 studies reported need for blood transfusion

  • 16/18 studies reported duration of surgery

  • 11/18 studies reported duration of hospital stay (days)

  • 5/18 studies reported postoperative haemoglobin

  • 5/18 studies reported postoperative haemoglobin drop

  • 8/18 reported postoperative morbidity

  • 1/18 reported pregnancy rate following surgery

  • 0/18 reported cost of intervention

Excluded studies

Twenty‐three studies were excluded from the review, for the following reasons:

  • 10/23 were not RCTs;

  • 13/23 had ineligible control groups.

Risk of bias in included studies

We have summarised our risk of bias assessments in Figure 2 and Figure 3.

Allocation

Ten studies were at low risk of selection bias related to sequence generation as they used computer randomisation or a random numbers table. The other eight studies did not describe the method used and were at unclear risk of this bias. Ten studies were at low risk of selection bias related to allocation concealment as they used adequate allocation concealment methods such as sequentially numbered opaque sealed envelopes. The other eight studies did not describe the method used and were at unclear risk of this bias.

Blinding

Blinding of participants and personnel

We did not consider that blinding was likely to influence findings for the primary review outcome (blood loss and need for blood transfusion). However, for secondary outcomes such as operative difficulties, postoperative morbidity including subjective outcomes such as severe pain, as well as tolerability and safety, blinding status could potentially affect the findings. Twelve studies described the use of a double‐dummy placebo that was identical to the intervention and were thus deemed to be at low risk of performance bias. The other six studies were considered to be at high risk of performance bias because either the care givers and patients were not blinded or because there were no placebo control groups.

Blinding of outcome assessors

Nine studies described blinding of outcome assessors and we judged them to be at low risk of detection bias. Two studies were judged to be at high risk of detection bias because the outcome assessors were not blinded. The other seven studies did not describe the blinding of assessors and were at unclear risk of this bias.

Incomplete outcome data

Sixteen studies analysed all or most (> 95%) of the women that were randomised and we judged them to be at low risk of bias. Two studies were considered to be at high risk of attrition bias: in both studies some participants (6.7% in one study and 8.3% in the other) were excluded after randomisation.

Selective reporting

We did not have access to the study protocols and therefore could not judge whether the studies reported all planned outcomes. The trial on mesna versus placebo did not report blood loss. The trials on bupivacaine plus epinephrine, chemical dissection with mesna, myoma morcellation, temporary clipping of the uterine artery and fibrin sealant patch did not report the need for blood transfusion. Trials on bupivacaine plus epinephrine, mesna, myoma morcellation, temporary clipping of uterine artery and fibrin sealant patch did not report on the adverse effects.

Other potential sources of bias

In one study (Taylor 2005) there was a substantial baseline difference in age between the two groups and the risk of bias was deemed high. We found no potential sources of within‐study bias in the other 17 studies.

Effects of interventions

See: Summary of findings for the main comparison Interventions to reduce blood loss during myomectomy for fibroids compared to placebo or no treatment; Summary of findings 2 Misoprostol compared to placebo to reduce blood loss during myomectomy for fibroids; Summary of findings 3 Vasopressin versus placebo to reduce blood loss during myomectomy for fibroids; Summary of findings 4 Bupivicaine plus epinephrine compared to placebo to reduce blood loss during myomectomy for fibroids; Summary of findings 5 Peri‐cervical tourniquet compared to no treatment to reduce blood loss during myomectomy for fibroids; Summary of findings 6 Gelatin‐thrombin matrix compared to placebo or no treatment to reduce blood loss during myomectomy for fibroids; Summary of findings 7 Ascorbic acid compared to no treatment to reduce blood loss during myomectomy for fibroids

summary of findings Table for the main comparison presents the effects of different interventions on blood loss during myomectomy.

1. Comparision of misoprostol versus placebo

Primary outcomes
1.1. Blood loss

Misoprostol was associated with significant reduction in blood loss compared to placebo (2 RCTs, 89 women: MD ‐97.88 ml, 95% CI ‐125.52 to ‐70.24; I2 = 43%; moderate‐quality evidence; Analysis 1.1; summary of findings Table 2).

A subgroup analysis showed a significant reduction in blood loss in both the abdominal myomectomy group (1 RCT, 25 women: MD ‐149.00 ml, 95% CI ‐229.24 to ‐ 68.76) and the laparoscopic myomectomy group (1 RCT, 64 women: MD ‐91.00 ml, 95% CI ‐120.44 to ‐61.56).

1.2. Need for blood transfusion

One trial involving 25 women found no evidence of effect of misoprostol on the need for blood transfusion (OR 0.36, 95% CI 0.05 to 2.50), and no woman needed a blood transfusion in the second trial involving 64 women (Analysis 1.2). We judged the quality of the evidence on the effect of misoprostol on the need for blood transfusion as low (summary of findings Table 2).

Secondary outcomes
1.3. Postoperative haemoglobin

Misoprostol was associated with higher postoperative haemoglobin compared to placebo (2 RCTs, 89 women: MD 0.69 g/dl, 95 CI 0.37 to 1.02; I2 = 0%; Analysis 1.4).

1.4. Duration of surgery

There was no evidence that the use of misoprostol changed the duration of surgery (summary of findings Table 2). The results were not pooled as pooling led to substantial heterogeneity (I2 = 88%), which could be explained by the fact that in one study myomectomy was achieved by laparotomy and in the other study myomectomy was performed by laparoscopy.

A subgroup analysis showed a significant reduction of blood loss in the abdominal myomectomy group (1 RCT, 25 women: OR ‐9.50, 95% CI ‐15.90 to ‐3.10) but not in the laparoscopic myomectomy group (1 RCT, 64 women: OR 9.00 min, ‐1.63 to 19.63).

1.5. Duration of hospital stay

There was no evidence of effect on the duration of hospital stay (1 RCT, 25 women: MD 0.00 days, 95% CI ‐0.82 to 0.82; Analysis 1.5).

1.6. Postoperative morbidity

There was no evidence of effect on febrile morbidity compared to placebo (2 RCTs, 89 women: OR 0.94, 95% CI 0.23 to 3.88; I2 = 0%; Analysis 1.7).

2. Vasopressin versus placebo

Primary outcomes
2.1. Blood loss

There was significant heterogeneity between the studies that assessed the effect of vasopressin. The heterogeneity between studies could be explained by the fact that in one study women had laparoscopic myomectomy and in two other studies the women had open abdominal myomectomy.

A subgroup analysis revealed that when compared to placebo, vasopressin was associated with significant reduction in blood loss during abdominal myomectomy (1 RCT, 20 women: MD ‐450 ml, 95% CI ‐507.49 to ‐392.51) as well as during laparoscopic myomectomy (2 RCTs, 108 women: MD ‐147.95 ml, 95% CI ‐174.17 to ‐121.73; I2 = 0%; Analysis 2.1).

2.2. Need for blood transfusion

Vasopressin was associated with a reduction in the need for blood transfusion compared to placebo (2 RCTs, 90 women: OR 0.15, 95% CI 0.03 to 0.74; I2 = 0%; moderate‐quality evidence; Analysis 2.2) (summary of findings Table 3).

A subgroup analysis showed no significant reduction in the need for blood transfusion in both the abdominal myomectomy group (1 RCT, 20 women: OR 0.11, 95% CI 0.01 to 1.24) and laparoscopic myomectomy group (1 RCT, 70 women: OR 0.18, 95% CI 0.02 to 1.60).

Secondary outcomes
2.3. Pregnancy (if desired)

There was no evidence of a difference in pregnancy one year after myomectomy between vasopressin and placebo (1 RCT, 38 women: OR 0.64, 95% CI 0.18 to 2.31; Analysis 2.6).

2.4. Duration of surgery

Vasopressin was associated with a reduction in the operating time compared to placebo (2 RCTs, 108 women: MD ‐27.72 min, 95% CI ‐35.82 to ‐19.61; I2 = 0%; moderate‐quality evidence; Analysis 2.3) (summary of findings Table 3).

2.5. Length of hospital stay

There was no evidence of a difference in the length of hospital stay between vasopressin and placebo (2 RCTs, 108 women: MD 0.11 days, 95% CI ‐0.69 to 0.91; P = 0.96; I2 = 75%; Analysis 2.4).

2.6. Conversion of laparoscopy to laparotomy

Compared to placebo, there was no evidence of an effect of vasopressin on conversion of laparoscopy to laparotomy (1 RCT, 70 women: OR 7.65, 95% CI 0.38 to 153.75; Analysis 2.7).

2.7. Postoperative adhesions

Compared to placebo, there was no evidence of an effect of vasopressin on postoperative adhesions (1 RCT, 38 women: OR 2.02, 95% CI 0.54 to 7.49; Analysis 2.5).

3. Bupivacaine plus epinephrine versus placebo

Primary outcomes
3.1. Blood loss

Compared to placebo, bupivacaine plus epinephrine significantly reduced blood loss (1 RCT, 60 women: MD ‐68.6 ml, 95% CI ‐93.69 to ‐43.51; low‐quality evidence; Analysis 3.1) (summary of findings Table 4).

3.2. Need for blood transfusion

The need for blood transfusion was not reported by investigators.

Secondary outcomes
3.3. Duration of surgery

Bupivicaine plus epinephrine was associated with a reduction in the operating time compared to placebo (1 RCT, 60 women: MD ‐30.50 min, 95% CI ‐37.68 to ‐23.32; low‐quality evidence; Analysis 3.2) (summary of findings Table 4).

3.4. Other secondary outcomes

Other secondary outcomes were not reported by investigators.

4. Peri‐cervical tourniquet versus no treatment

Primary outcomes
4.1. Blood loss

There was significant heterogeneity between studies that evaluated the effect of a peri‐cervical tourniquet (I2 = 95%; Analysis 4.1). Due to the significant heterogeneity between the studies, the studies were not combined. We attributed the heterogeneity between studies to the different methods used for the peri‐cervical tourniquet. One study (Taylor 2005) used a polyglactin suture tied around the cervix to occlude the uterine artery and left there after surgery, plus a polythene tourniquet tied round the infundibulopelvic ligament and removed after the operation. This study found a significant effect in blood loss, favouring the use of the tourniquet (1 RCT, 28 women: MD ‐1870.0, 95% CI ‐2547.16 to ‐1192.84; low‐quality evidence ). The other study (Ikechebelu 2010) used a Foley catheter that was tied round the base of the uterus and was released intermittently during surgery; and also revealed evidence that a peri‐cervical tourniquet reduced blood loss compared to no treatment (1 RCT, 93 women: MD ‐240.70, 95% CI ‐359.61 to ‐121.79; low‐quality evidence).

4.2. Need for blood transfusion

Peri‐cervical tourniquet was associated with a significantly reduced need for blood transfusion compared to placebo (1 RCT, 98 women: OR 0.22, 95% CI 0.09 to 0.55; low‐quality evidence). The use of a tourniquet around both the cervix and the infundibulopelvic ligament also significantly reduced blood loss (1 RCT, 28 women: OR 0.02, 95% CI 0.00 to 0.23; low‐quality evidence).

Secondary outcomes
4.3. Duration of surgery

There was no evidence of an effect on operating time with a peri‐cervical tourniquet compared to no treatment (1 RCT, 28 women: MD ‐4.00 min, 95% CI ‐29.28 to 21.28; low quality evidence; Analysis 4.3) (summary of findings Table 5).

4.4. Postoperative morbidity

Peri‐cervical tourniquet had no evidence of an effect on postoperative morbidity (Analysis 4.4): fever (1 RCT, 93 women: OR 1.09, 95% CI 0.46 to 2.59; Analysis 4.4), anaemia (1RCT, 93 women: OR 1.09, 95% CI 0.46 to 2.59), urinary tract infection (1 RCT, 93 women: OR 0.71, 95% CI 0.13 to 3.70), prolonged vaginal bleeding (1 RCT, 93 women: OR 2.21, 95% CI 0.09 to 55.82), pelvic abscess (1 RCT, 93 women: OR 2.21, 95% CI 0.09 to 55.82), and intestinal obstructions (1 RCT, 93 women: OR 2.21, 95% CI 0.09 to 55.82).

5. Oxytocin versus placebo

Primary outcomes
5.1. Blood loss

The effect of oxytocin on blood loss compared to placebo was inconsistent with significant heterogeneity across studies. There was no obvious explanation for the heterogeneity. A subgroup analysis revealed a reduction in blood loss when oxytocin was used in laparoscopic myomectomy (1 RCT, 60 women: MD ‐175.50 ml, 95% CI ‐301.01 to ‐49.93) but not open abdominal myomectomy (1 RCT, 94 women: MD 57.00 ml, 95% CI ‐129.22 to 243.22; Analysis 5.1).

5.2. Need for blood transfusion

Oxytocin did not appear to have an effect on the need for blood transfusion (2 RCTs, 154 women: OR 0.54, 95% CI 0.03 to 8.51; I2 = 89%; Analysis 5.2).

Secondary outcomes
5.3. Duration of surgery

Oxytocin had no significant effect on the operating time (2 RCTs, 154 women: MD 3.5 min, 95% CI ‐1.88 to 8.88; I2 = 0%; Analysis 5.3).

5.4. Postoperative hospital stay

Compared to placebo, oxytocin significantly reduced the duration of postoperative hospital stay (1 RCT, 60 women: MD ‐0.60 days, 95% CI ‐1.19 to ‐0.01; Analysis 5.5).

5.5. Postoperative morbidity

There was no evidence of an effect on postoperative morbidity by oxytocin compared to placebo (1 RCT, 60 women: OR 1.00, 95% CI 0.06 to 16.76; Analysis 5.5).

6. Mesna versus placebo

Primary outcomes
6.1. Blood loss

Blood loss was not reported by the investigators (Benassi 2000).

6.2. Need for blood transfusion

The need for blood transfusion was not reported by the investigators (Benassi 2000).

Secondary outcomes
6.3. Postoperative haemoglobin and haematocrit

Postoperative haemoglobin (1 RCT, 58 women: MD 0.50 g/dl, 95% CI 0.42 to 0.58; Analysis 6.3) and haematocrit (1 RCT, 58 women: MD 1.90%, 95% CI 1.30 to 2.50; Analysis 6.4) were significantly higher with mesna compared to placebo.

6.4. Duration of surgery

Chemical dissection with mesna was associated with a reduction in the operating time compared to placebo (1 RCT, 58 women: MD ‐20 min, 95% CI ‐28.64 to ‐11.36; Analysis 6.1).

6.4. Postoperative morbidity

There was no evidence of an effect on the incidence of postoperative fever by mesna compared to placebo (1 RCT, 58 women: OR 0.14, 95% CI 0.02 to 1.22; Analysis 6.5).

6.5. Length of hospital stay

Mesna was associated with a reduction in length of hospital stay compared to placebo (1 RCT, 58 women: MD ‐ 1.00 day, 95% CI ‐1.12 to ‐0.88; Analysis 6.2).

7. Myoma enucleation by morcellation versus no treatment

Primary outcomes
7.1. Blood loss

Myoma enucleation by morcellation did not have a significant effect on blood loss during laparoscopic myomectomy (1 RCT, 48 women: MD 65.40 ml, 95% CI ‐36.47 to 167.27; Analysis 7.1).

7.2. Need for blood transfusion

The need for blood transfusion was not reported by the investigators (Sinha 2005).

Secondary outcomes
7.3. Duration of surgery

Myoma morcellation was associated with a reduction in the operating time compared to placebo (1 RCT, 48 women: MD ‐25.30 min, 95% CI ‐44.23 to ‐6.37; Analysis 8.3).

7.4. Length of hospital stay

Myoma morcellation did not show a significant effect on the length of hospital stay (1 RCT, 48 women: MD ‐0.07 days, 95% CI ‐0.18 to 0.04; Analysis 7.3).

8. Tranexamic acid versus placebo

Primary outcomes
8.1. Blood loss

Intravenous tranexamic acid reduced blood loss during myomectomy compared to placebo (1 RCT, 100 women: MD ‐243 ml, 95% CI ‐460.02 to ‐25.98; Analysis 8.1).

8.2. Need for blood transfusion

Tranexamic acid did not have a significant effect on the need for blood transfusion (1 RCT, 100 women: OR 1.71, 95% CI 0.63 to 4.30; Analysis 8.2).

Secondary outcomes
8.3. Postoperative haemoglobin and haematocrit

There was no evidence of effect by tranexamic acid compared to placebo on postoperative haemoglobin (1 RCT, 100 women: MD 0.21 g/dl, 95% CI ‐0.36 to 0.78; Analysis 8.4) and haematocrit (1 RCT, 100 women: MD 1.00%, 95% CI ‐0.43 to 2.43; Analysis 8.5).

8.4 Duration of surgery

Tranexamic acid was associated with a reduction in the operating time compared to placebo (1 RCT, 100 women: MD ‐11 min, 95% CI ‐21.09 to ‐0.91; Analysis 8.3).

9. Gelatin‐thrombin matrix versus placebo or no treatment

Primary outcomes
9.1. Blood loss

Compared to no treatment, the application of a gelatin‐thrombin matrix on the uterine incision reduced blood loss during myomectomy (1 RCT, 50 women: MD ‐545.00 ml, 95% CI ‐593.26 to ‐496.74; low‐quality evidence; Analysis 9.1) (summary of findings Table 6) and postoperative vaginal blood loss (1 RCT, 50 women: MD ‐225.00 ml, 95% CI ‐254.46 to ‐195.54; Analysis 9.3).

9.2. Need for blood transfusion

Gelatin‐thrombin matrix reduced the need for blood transfusion compared to no treatment (1 RCT, 100 women: OR 0.01, 95% CI 0.00 to 0.10; low‐quality evidence; Analysis 9.2) (summary of findings Table 6).

Secondary outcomes
9.3. Postoperative haemoglobin and haematocrit

Gelatin‐thrombin matrix reduced the drop in haemoglobin after surgery compared to no treatment (1 RCT, 50 women: MD ‐2.30 g/dl, 95% CI ‐2.66 to ‐1.94; Analysis 9.5).

9.4. Duration of surgery

Gelatin‐thrombin was associated with an increase in the operating time compared to no treatment (1 RCT, 50 women: MD 5.00 min, 95% CI 1.29 to 8.71; low‐quality evidence; Analysis 9.4) (summary of findings Table 6).

9.4. Length of hospital stay

Gelatin‐thrombin matrix reduced the duration of hospital stay compared to no treatment (1 RCT, 50 women: MD ‐2.00 days, 95% CI ‐2.69 to ‐1.31; Analysis 9.6).

9.5. Postoperative morbidity

There was no evidence of an effect on postoperative fever by gelatin‐thrombin matrix compared to no treatment (1 RCT, 50 women: OR 0.32, 95% CI 0.01 to 8.25; Analysis 9.7).

10. Ascorbic acid versus no treatment

Primary outcomes
10.1. Blood loss

Compared to no treatment, the administration of ascorbic acid during myomectomy reduced blood loss (1 RCT, 102 women: MD ‐411.46 ml, 95% CI ‐502.58 to ‐320.34; P < 0.00001; low‐quality evidence; Analysis 10.1) (summary of findings Table 7).

10.2. Need for blood transfusion

There was no evidence that ascorbic acid had an effect on the need for blood transfusion compared to no treatment (1 RCT, 102 women: OR 0.38, 95% CI 0.11 to 1.32; P = 0.13; very low‐quality evidence).

Secondary outcomes
10.3. Postoperative haemoglobin and haematocrit

There was evidence that, compared to no treatment, ascorbic acid reduced the drop in postoperative haematocrit (1 RCT, 102 women: MD ‐0.70%, 95% CI ‐1.34 to ‐0.06; P = 0.03) but not the drop in postoperative haemoglobin (1 RCT, 102 women: MD 0.14 g/dl, 95% CI ‐0.22 to 0.50; P = 0.44).

10.4. Duration of surgery

Ascorbic acid reduced the operating time compared to no treatment (1 RCT, 102 women: MD ‐26.00 min, 95% CI ‐33.10 to ‐18.90; P < 0.00001; low‐quality evidence).

10.5. Duration of hospital stay

Compared to no treatment, there was evidence that ascorbic acid reduced the duration of hospital stay (1 RCT, 102 women: MD ‐0.4 days, 95% CI ‐0.65 to ‐0.15; P = 0.002).

10.6. Postoperative morbidity

Overall, there was no evidence of an effect on postoperative morbidity by ascorbic acid compared to no treatment (1 RCT, 102 women: OR 1.64, 95% CI 0.71 to 3.82; P = 0.25), which included postoperative fever (OR 1.88, 95% CI 0.58 to 6.07; P = 0.29), vomiting (OR 1.96, 95% CI 0.17 to 22.32; P = 0.59), constipation (OR 0.31, 95% CI 0.01 to 7.90; P = 0.48) and severe pain (OR 2.00, 95 CI 0.36 to 11.44; P = 0.44).

11. Dinoprostone versus placebo or no treatment

Primary outcomes
11.1. Blood loss

Compared to placebo, a dinoprostone vaginal suppository administered before myomectomy reduced blood loss (1 RCT, 108 women: MD ‐131.60 ml, 95% CI ‐253.42 to ‐9.78; P = 0.03; Analysis 11.1).

11.2. Need for blood transfusion

Diniprostone reduced the need for blood transfusion compared to placebo (1 RCT, 108 women: OR 0.17, 95% CI 0.04 to 0.81; P = 0.61; low‐quality evidence).

Secondary outcomes
11.3. Postoperative haemoglobin and haematocrit

Compared to a placebo, dinoprostone reduced the drop in postoperative haemoglobin (1 RCT, 108 women: MD ‐0.50, 95% CI ‐0.88 to ‐0.12; P = 0.009), but had no effect on postoperative haematocrit (1 RCT, 108 women: MD 0.10, 95% CI ‐0.39 to 0.59; P = 0.69).

11.4. Duration of surgery

Compared to placebo, dinoprostone had no effect on the operating time (1 RCT, 108 women: MD ‐2.60 min, 95% CI ‐12.55 to 7.35; P = 0.25).

11.5. Length of hospital stay

There was no evidence of an effect on the duration of hospital stay by dinoprostone compared to no treatment (1 RCT, 108 women: MD 0.30 days, 95% CI ‐0.22 to 0.82; P = 0.25).

11.6. Postoperative morbidity

There was no evidence of an effect on postoperative fever by dinoprostone compared to no treatment (OR 1.53, 95% CI 0.25 to 9.54; P = 0.65).

12. Loop ligation of myoma pseudocapsule combined with vasopressin versus no treatment

12.1. Blood loss

Compared to no treatment, loop ligation of the myoma pseudocapsule during myomectomy reduced blood loss (1 RCT, 70 women: MD ‐305.01 ml, 95% CI ‐354.83 to ‐255.19; P < 0.00001; Analysis 12.1).

12.2. Need for blood transfusion

Compared to no treatment, loop ligation of the myoma pseudocapsule had no effect on the need for blood transfusion (1 RCT, 70 women: OR 0.08, 95% CI 0.00 to 1.47; P = 0.09).

Secondary outcomes
12.3. Duration of surgery

Loop ligation of the myoma pseudocapsule significantly reduced the operating time (1 RCT, 70 women: MD ‐32.76 min, 95% CI ‐40.81 to ‐24.71; P < 0.00001).

12.4. Length of hospital stay

Compared to no treatment, loop ligation of the myoma pseudocapsule significantly reduced the duration of hospital stay (1 RCT, 70 women: MD ‐1.46 days, 95% CI ‐1.85 to ‐1.07; P < 0.00001).

13. Temporary clipping of uterine artery versus no treatment

13.1. Blood loss

This outcome was not reported by the investigators.

13.2. Need for blood transfusion

No patient required blood transfusion.

Secondary outcomes
13.3. Postoperative haemoglobin and haematocrit

We found no evidence of an effect on postoperative haemoglobin by the temporary clipping of the uterine artery compared to no treatment (1 RCT, 166 women: MD ‐2.25 g/dl, 95% CI ‐0.61 to 0.11; P = 0.17).

13.4. Duration of surgery

The temporary clipping of the uterine artery significantly increased the operating time (1 RCT, 166 women: MD 40.00 min, 95% CI 30.01 to 49.99; P < 0.00001).

13.5. Length of hospital stay

We found no evidence of an effect on the duration of hospital stay by the temporary clipping of the uterine artery compared to no treatment (1 RCT, 70 women: MD 0.00 days, 95% CI ‐0.15 to 0.15; P = 1.00).

13.6. Postoperative morbidity

We found no evidence of an effect on postoperative morbidity by the temporary clipping of the uterine artery compared to no treatment (1 RCT, 166 women: OR 1.95, 95% CI 0.79 to 4.79; P = 0.14).

14. Fibrin sealant patch versus no treatment

14.1. Blood loss

Compared to no treatment, the application of a fibrin sealant patch (surgical collagen patch or sponge coated with thrombin and fibrinogen to stop local bleeding) on the uterus reduced blood loss during myomectomy (1 RCT, 70 women: MD ‐26.50 ml, 95% CI ‐44.46 to ‐8.53; P = 0.004; Analysis 14.1) and postoperative blood loss in the drainage bag (1 RCT, 70 women: MD ‐44.60 ml, 95% CI ‐65.06 to ‐24.14; P < 0.0001).

14.2. Need for blood transfusion

No patient required blood transfusion.

Secondary outcomes
14.3. Pregnancy (if desired)

We found no evidence of an effect on conception after myomectomy by the fibrin sealant patch compared to no treatment (1 RCT, 70 women: OR 3.16, 95% CI 0.76 to 13.11; P = 0.11).

14.4. Duration of surgery

We found no evidence of an effect on the operating time by fibrin sealant patch compared to no treatment (1 RCT, 70 women: MD ‐0.4 min, 95% CI ‐4.47 to 3.67; P = 0.85).

14.5. Length of hospital stay

We found no effect of the fibrin sealant patch on the duration of hospital stay (1 RCT, 70 women: MD 0.00 days, 95% CI ‐0.09 to 0.09; P = 1.00).

15. Other analysis

Where data were available, we performed subgroup analyses based on the technique of myomectomy (Analysis 1.1; Analysis 1.3; Analysis 2.1; Analysis 2.2). The use of a random‐effects model compared to a fixed‐effect model made no difference. All other planned subgroup and sensitivity analyses were not conducted due to insufficient data.

Discussion

Summary of main results

This review has evaluated the effect of different interventions on blood loss during myomectomy for uterine fibroids. There are a few well designed randomised trials that have assessed the effect of each intervention on blood loss. Compared to placebo or no treatment, misoprostol, vasopressin, bupivacaine plus epinephrine, tranexamic acid, gelatin‐thrombin matrix, peri‐cervical tourniquet, tourniquet round both cervix and infundibulopelvic ligament, mesna, ascorbic acid, dinoprostone, loop ligation of the myoma pseudocapsule and a fibrin sealant patch (collagen sponge with thrombin and fibrinogen) were found to significantly reduce bleeding during myomectomy. In contrast, oxytocin, myoma morcellation and temporary clipping of the uterine artery did not significantly reduce blood loss when compared to placebo or no treatment.

Utero‐tonics

Some interventions have shown promising effects on reducing blood loss during myomectomy. Both misoprostol (MD ‐97.88 ml, 95% CI ‐125.52 to ‐70.24) and dinoprostone (MD ‐131.60 ml, 95% CI ‐253.42 to ‐9.78), prostaglandin E2 analogues, were shown to significantly reduce blood loss, probably by causing uterine contraction and reducing uterine blood flow. The trials on oxytocin, a known utero‐tonic agent, showed no statistically significant effect on blood loss during myomectomy.

Pharmacologic manipulation of the coagulation cascade

Similarly to prostaglandin E2 analogues, tranexamic acid (MD ‐243 ml, 95% CI ‐460.02 to ‐25.98) was found to significantly reduce blood loss during myomectomy. Tranexamic acid is an antifibrinolytic agent that acts by blocking the lysine‐binding site on plasmin thereby inhibiting fibrinolysis, the process wherein a fibrin clot, the product of coagulation, is broken down. Tranexamic acid has been used in clinical settings since the 1960s and has been found to reduce blood loss and the need for blood transfusion in cardiac surgery, liver transplantation and orthopaedic surgery (Dunn 1999).

The application of gelatin‐thrombin haemostatic sealant (MD ‐545.00 ml, 95% CI ‐593.26 to ‐496.74), a matrix of cross‐linked bovine‐derived gelatin granules and a bovine‐derived thrombin component, on the site of uterine incision significantly reduced blood loss during surgery and the need for blood transfusion. The gelatin matrix is hydrophilic and therefore adheres very well to wet tissue. The matrix activates the coagulation cascade and causes haemostasis.

The application of a fibrin sealant patch (MD ‐26.50 ml, 95% CI ‐44.47 to ‐8.53), which is a surgical patch coated with human coagulation factors fibrinogen and thrombin, significantly reduced blood loss during myomectomy.

Ascorbic acid (MD ‐411.46 ml, 95% CI ‐502.58 to ‐320.34) significantly reduced blood loss during myomectomy. Ascorbic acid (vitamin C) has important functions in platelets. During the first phase of haemostasis platelets are activated and aggregate to form a haemostasis plug. Ascorbic acid is water‐soluble and is not stored in the body, and when depleted the bleeding tendency increases due to dysfunctional connective tissue production in the blood vessel wall.

Interventions on the uterine artery

We found a significant reduction in intraoperative blood loss when vasopressin (MD ‐245.87 ml, 95% CI ‐434.58 to ‐57.16) is injected into the uterine muscles overlying the myoma during myomectomy. The injection of bupivacaine plus epinephrine into the myometrium overlying the myoma was evaluated in one study and the result showed evidence of a reduction in blood loss, although this might not be clinically significant (68.6 ml). Both vasopressin and bupivacaine plus epinephrine are known local vasoconstrictors and may reduce local blood flow when injected around the myoma.

A peri‐cervical tourniquet and use of a tourniquet round both the cervix and the infundibulopelvic ligament also significantly reduced blood loss during myomectomy, as anticipated. The uterus receives its blood supply primarily from the uterine artery and the occlusion of the uterine artery is expected to reduce blood loss by reducing blood flow to the uterus.However, there is no evidence that temporary clipping of the uterine artery reduce blood loss.

Chemical dissection of myoma

The study on the effect of chemical dissection of the myoma with mesna did not directly evaluate blood loss but showed a significant gain in postoperative haemoglobin levels. Mesna is a lytic agent that can disrupt connections between tissue layers (Denaro 2001) and may thus facilitate myoma enucleation. Similarly, we found that loop ligation of the myoma pseudocapsule during laparoscopic myomectomy significantly reduced blood loss.

Other outcomes

One way of evaluating the difficulties encountered during myomectomy was by measuring the operating time. Trials on vasopressin, bupivacaine plus epinephrine, mesna, tranexamic acid, ascorbic acid, myoma enucleation by morcellation, and loop ligation of the myoma pseudocapsule recorded a significant reduction in operating time. The use of misoprostol, oxytocin, peri‐cervical tourniquet, dinoprostone and a fibrin sealant patch showed no evidence of effect on the duration of surgery. The use of a gelatin‐thrombin matrix and the temporary clipping of the uterine artery increased the operating time.

Postoperative outcome was assessed by the duration of hospitalisation. A few trials included the duration of hospital stay in their evaluations. The trials on mesna, gelatin‐thrombin matrix, ascorbic acid and loop ligation of the myoma pseudocapsule recorded a significant decrease in the duration of hospital stay. No other trials found a significant effect on the duration of hospitalisation.

Overall completeness and applicability of evidence

Most comparisons included few trials with small sample sizes and insufficient power to detect moderate differences in blood loss. This review assessed only the effects of interventions versus placebo or no treatment. Head‐to‐head comparisons were not assessed by the review.

There are insufficient data on the adverse effects and costs of the different interventions. The trials on the gelatin‐thrombin matrix and ascorbic acid showed no significant difference in adverse effects between the intervention and the control groups. Most trials that commented on the adverse effects simply stated that there were no such effects recorded in the trial. Knowledge of these adverse events and the tolerability of the interventions is important because we have to make a trade off between the estimated benefits and the harms and costs before making any appropriate decisions about use or non‐use of any intervention. Nevertheless, evidence from clinical practice has shown that mesna is well tolerated and can be taken orally (Burkert 1983).

Quality of the evidence

The methodological quality of the included studies was generally good. The trials had small sample sizes (and, therefore, the effect sizes had large confidence intervals) and there was heterogeneity of effect between the included trials with several of the interventions. Despite the small sample sizes and heterogeneity of effect, there was a significant reduction in blood loss during myomectomy with 10 interventions when compared to placebo or no treatment.

  • Misoprostol and vasopressin: we rated each as moderate quality evidence because with both interventions the data were derived from two small studies and we could not rule out the possibility of publication bias.

  • Tranexamic acid, fibrin sealant patch, dinoprostone,peri‐cervical tourniquet and use of a tourniquet round both the cervix and the infundibulopelvic ligament : we rated each as low quality evidence because the data from each of the interventions were derived from one or two small studies and the pooled effect estimate was imprecise.

  • Ascorbic acid and loop ligation of myoma pseudocapsule: we rated each as low quality of evidence because with both interventions the data were derived from one small study and it was unclear how allocation concealment was done.

  • Bupivacaine plus epinephrine: we rated this as low quality evidence because the data were derived from one small study with a high risk of attrition bias (two patients in each arm did not receive the assigned intervention because of concomitant disease).

  • Gelatin‐thrombin matrix: we rated this as low quality evidence because the data were derived from one small study and it was unclear if the outcome assessors were blind.

Potential biases in the review process

Publication and selection biases are potential threats to all systematic reviews. We are confident that we have identified the existing clinical trials relevant to our question but cannot rule out the possibility that there are additional trials that are unpublished or published in sources not accessible to our search.

Agreements and disagreements with other studies or reviews

We are not aware of any reviews that have assessed the effectiveness of interventions to reduce haemorrhage during myomectomy. Evidence from this review supports findings previously reported in non‐randomised studies (McLaughin 1985; Baldoni 1995; Hutchins 1996; Dimitrov 1999).

The use of oxytocin showed no evidence of an effect on blood loss during myomectomy. This is consistent with other evidence that the myometrial concentration of oxytocin receptors is very low in non‐pregnant uteri (Fuchs 1984).

Flow diagram showing screening of search outputs and study selection.
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Figure 1

Flow diagram showing screening of search outputs and study selection.

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original image
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Figure 2
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Figure 3
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Comparison 1 Misoprostol versus placebo, Outcome 1 Blood loss (ml).
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Analysis 1.1

Comparison 1 Misoprostol versus placebo, Outcome 1 Blood loss (ml).

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Comparison 1 Misoprostol versus placebo, Outcome 2 Need for blood transfusion.
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Analysis 1.2

Comparison 1 Misoprostol versus placebo, Outcome 2 Need for blood transfusion.

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Comparison 1 Misoprostol versus placebo, Outcome 3 Duration of surgery (min).
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Analysis 1.3

Comparison 1 Misoprostol versus placebo, Outcome 3 Duration of surgery (min).

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Comparison 1 Misoprostol versus placebo, Outcome 4 Postoperative haemoglobin (g/dl).
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Analysis 1.4

Comparison 1 Misoprostol versus placebo, Outcome 4 Postoperative haemoglobin (g/dl).

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Comparison 1 Misoprostol versus placebo, Outcome 5 Duration of hospital stay (days).
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Analysis 1.5

Comparison 1 Misoprostol versus placebo, Outcome 5 Duration of hospital stay (days).

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Comparison 1 Misoprostol versus placebo, Outcome 6 Postoperative haemoglobin drop (g/dl).
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Analysis 1.6

Comparison 1 Misoprostol versus placebo, Outcome 6 Postoperative haemoglobin drop (g/dl).

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Comparison 1 Misoprostol versus placebo, Outcome 7 Postoperative complications.
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Analysis 1.7

Comparison 1 Misoprostol versus placebo, Outcome 7 Postoperative complications.

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Comparison 2 Vasopressin versus placebo, Outcome 1 Blood loss (ml).
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Analysis 2.1

Comparison 2 Vasopressin versus placebo, Outcome 1 Blood loss (ml).

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Comparison 2 Vasopressin versus placebo, Outcome 2 Need for blood transfusion.
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Analysis 2.2

Comparison 2 Vasopressin versus placebo, Outcome 2 Need for blood transfusion.

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Comparison 2 Vasopressin versus placebo, Outcome 3 Duration of surgery (min).
Figures and Tables -
Analysis 2.3

Comparison 2 Vasopressin versus placebo, Outcome 3 Duration of surgery (min).

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Comparison 2 Vasopressin versus placebo, Outcome 4 Duration of hospital stay (days).
Figures and Tables -
Analysis 2.4

Comparison 2 Vasopressin versus placebo, Outcome 4 Duration of hospital stay (days).

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Comparison 2 Vasopressin versus placebo, Outcome 5 Postoperative complications.
Figures and Tables -
Analysis 2.5

Comparison 2 Vasopressin versus placebo, Outcome 5 Postoperative complications.

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Comparison 2 Vasopressin versus placebo, Outcome 6 Pregnancy after myomectomy.
Figures and Tables -
Analysis 2.6

Comparison 2 Vasopressin versus placebo, Outcome 6 Pregnancy after myomectomy.

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Comparison 2 Vasopressin versus placebo, Outcome 7 Conversion of laparoscopy to laparotomy.
Figures and Tables -
Analysis 2.7

Comparison 2 Vasopressin versus placebo, Outcome 7 Conversion of laparoscopy to laparotomy.

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Comparison 3 Bupivicaine plus epinephrine versus placebo, Outcome 1 Blood loss (ml).
Figures and Tables -
Analysis 3.1

Comparison 3 Bupivicaine plus epinephrine versus placebo, Outcome 1 Blood loss (ml).

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Comparison 3 Bupivicaine plus epinephrine versus placebo, Outcome 2 Duration of surgery (min).
Figures and Tables -
Analysis 3.2

Comparison 3 Bupivicaine plus epinephrine versus placebo, Outcome 2 Duration of surgery (min).

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Comparison 4 Peri‐cervical tourniquet versus no treatment, Outcome 1 Blood loss (ml).
Figures and Tables -
Analysis 4.1

Comparison 4 Peri‐cervical tourniquet versus no treatment, Outcome 1 Blood loss (ml).

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Comparison 4 Peri‐cervical tourniquet versus no treatment, Outcome 2 Need for blood transfusion.
Figures and Tables -
Analysis 4.2

Comparison 4 Peri‐cervical tourniquet versus no treatment, Outcome 2 Need for blood transfusion.

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Comparison 4 Peri‐cervical tourniquet versus no treatment, Outcome 3 Duration of surgery (min).
Figures and Tables -
Analysis 4.3

Comparison 4 Peri‐cervical tourniquet versus no treatment, Outcome 3 Duration of surgery (min).

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Comparison 4 Peri‐cervical tourniquet versus no treatment, Outcome 4 Postoperative complications.
Figures and Tables -
Analysis 4.4

Comparison 4 Peri‐cervical tourniquet versus no treatment, Outcome 4 Postoperative complications.

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Comparison 5 Oxytocin versus placebo, Outcome 1 Blood loss (ml).
Figures and Tables -
Analysis 5.1

Comparison 5 Oxytocin versus placebo, Outcome 1 Blood loss (ml).

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Comparison 5 Oxytocin versus placebo, Outcome 2 Need for blood transfusion.
Figures and Tables -
Analysis 5.2

Comparison 5 Oxytocin versus placebo, Outcome 2 Need for blood transfusion.

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Comparison 5 Oxytocin versus placebo, Outcome 3 Duration of surgery (min).
Figures and Tables -
Analysis 5.3

Comparison 5 Oxytocin versus placebo, Outcome 3 Duration of surgery (min).

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Comparison 5 Oxytocin versus placebo, Outcome 4 Postoperative complications.
Figures and Tables -
Analysis 5.4

Comparison 5 Oxytocin versus placebo, Outcome 4 Postoperative complications.

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Comparison 5 Oxytocin versus placebo, Outcome 5 Duration of hospital stay (days).
Figures and Tables -
Analysis 5.5

Comparison 5 Oxytocin versus placebo, Outcome 5 Duration of hospital stay (days).

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Comparison 6 Chemical dissection with mesna versus placebo, Outcome 1 Duration of surgery (min).
Figures and Tables -
Analysis 6.1

Comparison 6 Chemical dissection with mesna versus placebo, Outcome 1 Duration of surgery (min).

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Comparison 6 Chemical dissection with mesna versus placebo, Outcome 2 Duration of hospital stay (days).
Figures and Tables -
Analysis 6.2

Comparison 6 Chemical dissection with mesna versus placebo, Outcome 2 Duration of hospital stay (days).

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Comparison 6 Chemical dissection with mesna versus placebo, Outcome 3 Postoperative haemoglobin (g/dl).
Figures and Tables -
Analysis 6.3

Comparison 6 Chemical dissection with mesna versus placebo, Outcome 3 Postoperative haemoglobin (g/dl).

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Comparison 6 Chemical dissection with mesna versus placebo, Outcome 4 Postoperative haematocrit.
Figures and Tables -
Analysis 6.4

Comparison 6 Chemical dissection with mesna versus placebo, Outcome 4 Postoperative haematocrit.

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Comparison 6 Chemical dissection with mesna versus placebo, Outcome 5 Postoperative complications.
Figures and Tables -
Analysis 6.5

Comparison 6 Chemical dissection with mesna versus placebo, Outcome 5 Postoperative complications.

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Comparison 7 Myoma morcellation versus standard technique of enucleation (no treatment), Outcome 1 Blood loss (ml).
Figures and Tables -
Analysis 7.1

Comparison 7 Myoma morcellation versus standard technique of enucleation (no treatment), Outcome 1 Blood loss (ml).

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Comparison 7 Myoma morcellation versus standard technique of enucleation (no treatment), Outcome 2 Duration of surgery (min).
Figures and Tables -
Analysis 7.2

Comparison 7 Myoma morcellation versus standard technique of enucleation (no treatment), Outcome 2 Duration of surgery (min).

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Comparison 7 Myoma morcellation versus standard technique of enucleation (no treatment), Outcome 3 Duration of hospital stay (days).
Figures and Tables -
Analysis 7.3

Comparison 7 Myoma morcellation versus standard technique of enucleation (no treatment), Outcome 3 Duration of hospital stay (days).

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Comparison 8 Intravenous injection of tranexamic acid versus placebo, Outcome 1 Blood loss (ml).
Figures and Tables -
Analysis 8.1

Comparison 8 Intravenous injection of tranexamic acid versus placebo, Outcome 1 Blood loss (ml).

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Comparison 8 Intravenous injection of tranexamic acid versus placebo, Outcome 2 Need for blood transfusion.
Figures and Tables -
Analysis 8.2

Comparison 8 Intravenous injection of tranexamic acid versus placebo, Outcome 2 Need for blood transfusion.

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Comparison 8 Intravenous injection of tranexamic acid versus placebo, Outcome 3 Duration of surgery (min).
Figures and Tables -
Analysis 8.3

Comparison 8 Intravenous injection of tranexamic acid versus placebo, Outcome 3 Duration of surgery (min).

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Comparison 8 Intravenous injection of tranexamic acid versus placebo, Outcome 4 Postoperative haemoglobin (g/dl).
Figures and Tables -
Analysis 8.4

Comparison 8 Intravenous injection of tranexamic acid versus placebo, Outcome 4 Postoperative haemoglobin (g/dl).

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Comparison 8 Intravenous injection of tranexamic acid versus placebo, Outcome 5 Postoperative haematocrit.
Figures and Tables -
Analysis 8.5

Comparison 8 Intravenous injection of tranexamic acid versus placebo, Outcome 5 Postoperative haematocrit.

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Comparison 9 Gelatin‐thrombin matrix versus placebo or no treatment, Outcome 1 Blood loss (ml).
Figures and Tables -
Analysis 9.1

Comparison 9 Gelatin‐thrombin matrix versus placebo or no treatment, Outcome 1 Blood loss (ml).

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Comparison 9 Gelatin‐thrombin matrix versus placebo or no treatment, Outcome 2 Need for blood transfusion.
Figures and Tables -
Analysis 9.2

Comparison 9 Gelatin‐thrombin matrix versus placebo or no treatment, Outcome 2 Need for blood transfusion.

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Comparison 9 Gelatin‐thrombin matrix versus placebo or no treatment, Outcome 3 Postoperative vaginal blood loss (ml).
Figures and Tables -
Analysis 9.3

Comparison 9 Gelatin‐thrombin matrix versus placebo or no treatment, Outcome 3 Postoperative vaginal blood loss (ml).

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Comparison 9 Gelatin‐thrombin matrix versus placebo or no treatment, Outcome 4 Duration of surgery (min).
Figures and Tables -
Analysis 9.4

Comparison 9 Gelatin‐thrombin matrix versus placebo or no treatment, Outcome 4 Duration of surgery (min).

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Comparison 9 Gelatin‐thrombin matrix versus placebo or no treatment, Outcome 5 Postoperative haemoglobin drop (g/dl).
Figures and Tables -
Analysis 9.5

Comparison 9 Gelatin‐thrombin matrix versus placebo or no treatment, Outcome 5 Postoperative haemoglobin drop (g/dl).

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Comparison 9 Gelatin‐thrombin matrix versus placebo or no treatment, Outcome 6 Duration of hospital stay (days).
Figures and Tables -
Analysis 9.6

Comparison 9 Gelatin‐thrombin matrix versus placebo or no treatment, Outcome 6 Duration of hospital stay (days).

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Comparison 9 Gelatin‐thrombin matrix versus placebo or no treatment, Outcome 7 Postoperative fever.
Figures and Tables -
Analysis 9.7

Comparison 9 Gelatin‐thrombin matrix versus placebo or no treatment, Outcome 7 Postoperative fever.

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Comparison 10 Ascorbic acid versus placebo or no treatment, Outcome 1 Blood loss (ml).
Figures and Tables -
Analysis 10.1

Comparison 10 Ascorbic acid versus placebo or no treatment, Outcome 1 Blood loss (ml).

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Comparison 10 Ascorbic acid versus placebo or no treatment, Outcome 2 Need for blood transfusion.
Figures and Tables -
Analysis 10.2

Comparison 10 Ascorbic acid versus placebo or no treatment, Outcome 2 Need for blood transfusion.

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Comparison 10 Ascorbic acid versus placebo or no treatment, Outcome 3 Duration of surgery (min).
Figures and Tables -
Analysis 10.3

Comparison 10 Ascorbic acid versus placebo or no treatment, Outcome 3 Duration of surgery (min).

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Comparison 10 Ascorbic acid versus placebo or no treatment, Outcome 4 Duration of hospital stay (days).
Figures and Tables -
Analysis 10.4

Comparison 10 Ascorbic acid versus placebo or no treatment, Outcome 4 Duration of hospital stay (days).

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Comparison 10 Ascorbic acid versus placebo or no treatment, Outcome 5 Posoperative haemoglobin drop (g/dl).
Figures and Tables -
Analysis 10.5

Comparison 10 Ascorbic acid versus placebo or no treatment, Outcome 5 Posoperative haemoglobin drop (g/dl).

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Comparison 10 Ascorbic acid versus placebo or no treatment, Outcome 6 Pospoerative hematocrit drop (%).
Figures and Tables -
Analysis 10.6

Comparison 10 Ascorbic acid versus placebo or no treatment, Outcome 6 Pospoerative hematocrit drop (%).

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Comparison 10 Ascorbic acid versus placebo or no treatment, Outcome 7 Posoperative complications.
Figures and Tables -
Analysis 10.7

Comparison 10 Ascorbic acid versus placebo or no treatment, Outcome 7 Posoperative complications.

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Comparison 11 Dinoprostone versus placebo, Outcome 1 Blood loss (ml).
Figures and Tables -
Analysis 11.1

Comparison 11 Dinoprostone versus placebo, Outcome 1 Blood loss (ml).

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Comparison 11 Dinoprostone versus placebo, Outcome 2 Need for blood transfusion.
Figures and Tables -
Analysis 11.2

Comparison 11 Dinoprostone versus placebo, Outcome 2 Need for blood transfusion.

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Comparison 11 Dinoprostone versus placebo, Outcome 3 Duration of surgery (min).
Figures and Tables -
Analysis 11.3

Comparison 11 Dinoprostone versus placebo, Outcome 3 Duration of surgery (min).

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Comparison 11 Dinoprostone versus placebo, Outcome 4 Duration of hospital stay (days).
Figures and Tables -
Analysis 11.4

Comparison 11 Dinoprostone versus placebo, Outcome 4 Duration of hospital stay (days).

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Comparison 11 Dinoprostone versus placebo, Outcome 5 Postoperative haemoglobin (g/dl).
Figures and Tables -
Analysis 11.5

Comparison 11 Dinoprostone versus placebo, Outcome 5 Postoperative haemoglobin (g/dl).

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Comparison 11 Dinoprostone versus placebo, Outcome 6 Postoperative haemoglobin drop (g/dl).
Figures and Tables -
Analysis 11.6

Comparison 11 Dinoprostone versus placebo, Outcome 6 Postoperative haemoglobin drop (g/dl).

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Comparison 11 Dinoprostone versus placebo, Outcome 7 Postoperative complications.
Figures and Tables -
Analysis 11.7

Comparison 11 Dinoprostone versus placebo, Outcome 7 Postoperative complications.

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Comparison 12 Loop ligation of myoma pseudocapsule plus vasopressin versus no treatment, Outcome 1 Blood loss (ml).
Figures and Tables -
Analysis 12.1

Comparison 12 Loop ligation of myoma pseudocapsule plus vasopressin versus no treatment, Outcome 1 Blood loss (ml).

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Comparison 12 Loop ligation of myoma pseudocapsule plus vasopressin versus no treatment, Outcome 2 Need for blood transfusion.
Figures and Tables -
Analysis 12.2

Comparison 12 Loop ligation of myoma pseudocapsule plus vasopressin versus no treatment, Outcome 2 Need for blood transfusion.

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Comparison 12 Loop ligation of myoma pseudocapsule plus vasopressin versus no treatment, Outcome 3 Duration of surgery (min).
Figures and Tables -
Analysis 12.3

Comparison 12 Loop ligation of myoma pseudocapsule plus vasopressin versus no treatment, Outcome 3 Duration of surgery (min).

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Comparison 12 Loop ligation of myoma pseudocapsule plus vasopressin versus no treatment, Outcome 4 Duration of hospital stay (days).
Figures and Tables -
Analysis 12.4

Comparison 12 Loop ligation of myoma pseudocapsule plus vasopressin versus no treatment, Outcome 4 Duration of hospital stay (days).

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Comparison 13 Temporary clipping of uterine artery versus no treatment, Outcome 1 Need for blood transfusion.
Figures and Tables -
Analysis 13.1

Comparison 13 Temporary clipping of uterine artery versus no treatment, Outcome 1 Need for blood transfusion.

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Comparison 13 Temporary clipping of uterine artery versus no treatment, Outcome 2 Duration of surgery (min).
Figures and Tables -
Analysis 13.2

Comparison 13 Temporary clipping of uterine artery versus no treatment, Outcome 2 Duration of surgery (min).

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Comparison 13 Temporary clipping of uterine artery versus no treatment, Outcome 3 Postoperative haemoglobin drop (g/dl).
Figures and Tables -
Analysis 13.3

Comparison 13 Temporary clipping of uterine artery versus no treatment, Outcome 3 Postoperative haemoglobin drop (g/dl).

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Comparison 13 Temporary clipping of uterine artery versus no treatment, Outcome 4 Duration of hospital stay (days).
Figures and Tables -
Analysis 13.4

Comparison 13 Temporary clipping of uterine artery versus no treatment, Outcome 4 Duration of hospital stay (days).

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Comparison 13 Temporary clipping of uterine artery versus no treatment, Outcome 5 Postoperative complications.
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Analysis 13.5

Comparison 13 Temporary clipping of uterine artery versus no treatment, Outcome 5 Postoperative complications.

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Comparison 14 Fibrin sealant patch versus no treatment, Outcome 1 Blood loss (ml).
Figures and Tables -
Analysis 14.1

Comparison 14 Fibrin sealant patch versus no treatment, Outcome 1 Blood loss (ml).

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Comparison 14 Fibrin sealant patch versus no treatment, Outcome 2 Postoperative blood loss in drainage bag.
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Analysis 14.2

Comparison 14 Fibrin sealant patch versus no treatment, Outcome 2 Postoperative blood loss in drainage bag.

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Comparison 14 Fibrin sealant patch versus no treatment, Outcome 3 Need for blood transfusion.
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Analysis 14.3

Comparison 14 Fibrin sealant patch versus no treatment, Outcome 3 Need for blood transfusion.

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Comparison 14 Fibrin sealant patch versus no treatment, Outcome 4 Duration of surgery (min).
Figures and Tables -
Analysis 14.4

Comparison 14 Fibrin sealant patch versus no treatment, Outcome 4 Duration of surgery (min).

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Comparison 14 Fibrin sealant patch versus no treatment, Outcome 5 Duration of hospital stay (days).
Figures and Tables -
Analysis 14.5

Comparison 14 Fibrin sealant patch versus no treatment, Outcome 5 Duration of hospital stay (days).

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Comparison 14 Fibrin sealant patch versus no treatment, Outcome 6 Conception after surgery.
Figures and Tables -
Analysis 14.6

Comparison 14 Fibrin sealant patch versus no treatment, Outcome 6 Conception after surgery.

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Summary of findings for the main comparison. Interventions to reduce blood loss during myomectomy for fibroids compared to placebo or no treatment

Interventions to reduce blood loss during myomectomy for fibroids compared to placebo or no treatment

Population: Women with fibroids
Settings: Various settings in low income, middle income, and high income countries
Intervention: Diverse interventions
Comparison: Placebo or no treatment

Intervention

Illustrative comparative risks (95% CI) on blood loss

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Placebo or no treatment

Interventions

Misoprostol in abdominal myomectomy

Mean blood loss with placebo was
621 ml

Mean blood loss with misoprostol was
149.00 ml lower
(229.24 to 68.76 lower)

MD ‐149.00 (‐229.24 to ‐68.76)

25
(1 study)

⊕⊕⊕⊝
moderate

We rated down the quality of evidence (by 1) because the data were derived from one small study

Misoprostol in laparoscopic myomectomy

Mean blood loss with placebo was
322.39 ml

Mean blood loss with misoprostol was
91.00 ml lower
(120.44 to 61.56 lower)

MD ‐91.00 (‐120.44 to ‐61.56)

64
(1 study)

⊕⊕⊕⊝
moderate

We rated down the quality of evidence (by 1) because the data were derived from one small study

Vasopressin

Mean blood loss with placebo was
483.09 ml

Mean blood loss with vasopressin was
245.87 ml lower
(434.58 to 57.16 lower)

MD ‐245.87 (‐434.58 to ‐57.16)

128
(3 studies)

⊕⊕⊕⊝
moderate

We rated down the quality of evidence (by 1) because the data were derived from three small studies

Bupivicaine plus epinephrine

Mean blood loss with placebo was
212.5 ml

Mean blood loss with bupivicaine‐epinephrine was
68.6 ml lower
(93.69 to 43.51 lower)

MD ‐68.60 (‐93.69, ‐43.51)

60
(1 study)

⊕⊕⊝⊝
low

We rated down the quality of evidence (by 2) because the data were derived from one small study, with a high risk of attrition bias (2 patients in each arm did not receive assigned intervention because of concomitant disease)

Intravenous injection of tranexamic acid

Mean blood loss with placebo was
1047 ml

Mean blood loss with tranexamic was
243 ml lower
(460.02 to 25.98 lower)

MD ‐243.00 (‐460.02 to ‐25.980

100
(1 study)

⊕⊕⊝⊝
low

We rated down the quality of evidence (by 2) because the data were derived from one small study and the pooled effect estimate was imprecise

Gelatin‐thrombin matrix

Mean blood loss with placebo was
625 ml

Mean blood loss with Gelatin‐thrombin was
545 ml lower
(593.26 to 496.74 lower)

MD ‐545.00 (‐593.26 to ‐496.74)

50
(1 study)

⊕⊕⊝⊝
low

We rated down the quality of evidence (by 2) because the data were derived from one small study, and it is unclear if outcome assessors were blind

Ascorbic acid

Mean blood loss with no treatment was
932.9 ml

Mean blood loss with ascorbic acid was
411.46 ml lower
(502.58 to 320.34 lower)

MD ‐411.46

(‐502.58 to ‐320.34)

102
(1 study)

⊕⊕⊝⊝
low

We rated down the quality of evidence (by 2) because the data were derived from one small study, and it is unclear how allocation concealment was done

Dinoprostone (prostaglandin E2 analogue)

Mean blood loss with placebo was
485.7 ml

Mean blood loss with dinoprostone was
131.6 ml lower
(253.42 to 9.78 lower)

MD ‐131.60

(‐253.42 to ‐9.78)

108
(1 study)

⊕⊕⊝⊝
low

We rated down the quality of evidence (by 2) because the data were derived from one small study, and the effect estimate has wide confidence intervals

Loop ligation of myoma pseudocapsule plus vasopressin

Mean blood loss with no treatment was
363.68 ml

Mean blood loss with loop ligation was
305.01 lower
(354.83 to 255.19 lower)

MD ‐305.01

(‐354.83 to ‐255.19)

70
(1 study)

⊕⊕⊝⊝
low

We rated down the quality of evidence (by 2) because the data were derived from one small study, and it is unclear how allocation concealment was done

Fibrin sealant patch (collagen sponge with thrombin and fibrinogen)

Mean blood loss with no treatment was
151.1 ml

Mean blood loss with tachosil was
26.5 ml lower
(44.47 to 8.53 lower)

MD ‐26.50

(‐44.47 to ‐8.53)

70
(1 study)

⊕⊕⊝⊝
low

We rated down the quality of evidence (by 2) because the data were derived from one small study, and the effect estimate has wide confidence intervals

CI: Confidence interval; MD: mean difference

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Figures and Tables -
Summary of findings for the main comparison. Interventions to reduce blood loss during myomectomy for fibroids compared to placebo or no treatment
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Summary of findings 2. Misoprostol compared to placebo to reduce blood loss during myomectomy for fibroids

Misoprostol compared to placebo to reduce blood loss during myomectomy for fibroids

Patient or population: Women with fibroids
Settings: Middle and high income countries
Intervention: Misoprostol
Comparison: Placebo

Outcomes

Illustrative comparative risks (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Placebo

Misoprostol

Blood loss (ml)
Estimated blood loss during myomectomy

The mean blood loss in placebo group was
322.39 ml

The mean blood loss in misoprostol group was
97.88 ml lower
(125.52 to 70.24 lower)

MD ‐97.88 (‐125.52 to ‐70.24)

89
(2 studies)

⊕⊕⊕⊝
moderate1

We rated down the quality of evidence (by 1) because the data were derived from two small studies and we could not rule out the possibility of publication bias

Need for blood transfusion
Number of participants who received blood transfusion

87 per 1000

31 per 1000
(4 to 217)

OR 0.36
(0.05 to 2.5)

89
(2 studies)

⊕⊕⊝⊝
low1

We rated down the quality of evidence (by 2) because (i) we could not conclusively rule out the possibility of publication bias and (ii) the pooled effect had wide confidence intervals

Duration of surgery (min)
Operative time

The mean duration of surgery in placebo group was
69.57 min for abdominal myomectomy and 77 min for laparoscopic myomectomy

The mean duration of surgery in misoprostol group was
9.50 min lower
(15.90 lower to 3.10 lower) in abdominal myomectomy and 9 min higher (1.63 lower to 19.63 higher) in laparoscopic myomectomy

MD ‐9.50

(‐15.90 to ‐3.10) for abdominal myomectomy &

MD 9.00

(‐1.63 to 19.63) for laparoscopic myomectomy

25
(1 study) for abdominal myomectomy &

64

(1 study) for laparoscopic myomectomy

⊕⊕⊝⊝
low1

We rated down the quality of evidence (by 2) because (i) we could not conclusively rule out the possibility of publication bias and (ii) the pooled effect had wide confidence intervals

We did not rate down the evidence due to heterogeneity because this could be explained by the type of myomectomy (laparoscopy versus laparotomy)

CI: Confidence interval; MD: mean difference; OR: Odds ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1In one trial the method of allocation concealment was not reported and in the other trial, allocation concealment was achieved using sequentially numbered opaque sealed envelopes.

Figures and Tables -
Summary of findings 2. Misoprostol compared to placebo to reduce blood loss during myomectomy for fibroids
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Summary of findings 3. Vasopressin versus placebo to reduce blood loss during myomectomy for fibroids

Vasopressin versus placebo to reduce blood loss during myomectomy for fibroids

Patient or population: Women with fibroids
Settings: Middle and low income countries
Intervention: Vasopressin
Comparison: Placebo

Outcomes

Illustrative comparative risks (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Placebo

Vasopressin

Blood loss (ml)
Estimated blood loss during myomectomy

The mean blood loss in the placebo groups was
483.09 ml

The mean blood loss in the vasopressin groups was
245.87 ml lower
(434.58 to 57.16 lower)

MD ‐245.87 (‐434.58 to ‐57.16)

128
(3 studies)

⊕⊕⊕⊝
moderate1

We rated down the quality of evidence (by 1) because the data were derived from three small studies and we could not rule out the possibility of publication bias

We did not rate down the evidence due to heterogeneity because this could be explained by the fact that in one study women had laparoscopic myomectomy and two other studies, women has open abdominal myomectomy

Need for blood transfusion
Participants who received blood transfusion

222 per 1000

33 per 1000
(7 to 164)

OR 0.15
(0.03 to 0.74)

90
(2 studies)

⊕⊕⊕⊝
moderate1

We rated down the quality of evidence (by 1) because the data were derived from two small studies and we could not rule out the possibility of publication bias

Duration of surgery
Operative time

The mean duration of surgery in the placebo groups was
111.45 min

The mean duration of surgery in the vasopressin groups was
27.72 min lower
(35.82 to 19.61 lower)

MD ‐27.72 (‐35.82 to ‐19.61)

108
(2 studies)

⊕⊕⊕⊝
moderate1

We rated down the quality of evidence (by 1) because the data were derived from two small studies and we could not rule out the possibility of publication bias

CI: Confidence interval; MD: mean difference; OR: Odds ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1In all the trials, allocation concealment was unclear.

Figures and Tables -
Summary of findings 3. Vasopressin versus placebo to reduce blood loss during myomectomy for fibroids
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Summary of findings 4. Bupivicaine plus epinephrine compared to placebo to reduce blood loss during myomectomy for fibroids

Bupivicaine plus epinephrine compared to placebo to reduce blood loss during myomectomy for fibroids

Patient or population: Women with fibroids
Settings: University hospital in Italy
Intervention: Bupivicaine plus epinephrine
Comparison: Placebo

Outcomes

Illustrative comparative risks (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Placebo

Bupivicaine plus epinephrine

Blood loss (ml)
Estimated blood loss during myomectomy

The mean blood loss in the placebo group was
212.5 ml

The mean blood loss in the bupivicaine‐epinephrine group was
68.6 ml lower
(93.69 to 43.51 lower)

MD ‐68.60 (‐93.69 to ‐43.51)

60
(1 study)

⊕⊕⊝⊝
low1

We rated down the quality of evidence (by 2) because the data were derived from one small study, with a high risk of attrition bias (2 patients in each arm did not receive assigned intervention because of concomitant disease)

Need for blood transfusion

Participants who received blood transfusion

Outcome not reported by investigators

Duration of surgery (min)
Operative time

The mean duration of surgery in the placebo group was
109.2 min

The mean duration of surgery in the bupivicaine‐epinephrine group was
30.50 min lower
(37.68 to 23.32 lower)

MD ‐30.50 (‐37.68 to ‐23.32)

60
(1 study)

⊕⊕⊝⊝
low1

We rated down the quality of evidence (by 2) because the data were derived from one small study, with a high risk of attrition bias (2 patients in each arm did not receive assigned intervention because of concomitant disease)

CI: Confidence interval; MD: mean difference

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1The allocation concealment was achieved by envelopes containing computer‐generated random numbers.

Figures and Tables -
Summary of findings 4. Bupivicaine plus epinephrine compared to placebo to reduce blood loss during myomectomy for fibroids
Navigate to table in Review
Summary of findings 5. Peri‐cervical tourniquet compared to no treatment to reduce blood loss during myomectomy for fibroids

Peri‐cervical tourniquet compared to no treatment to reduce blood loss during myomectomy for fibroids

Patient or population: Women with fibroids
Settings: Low and high income countries
Intervention: Tourniquet around the cervix only, or around both the cervix and the infundibulopelvic ligament
Comparison: No treatment

Outcomes

Illustrative comparative risks (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

No treatment

Peri‐cervical tourniquet

Blood loss (ml)
Estimated blood loss during myomectomy

The mean blood loss in the control groups was
756.4 ml (for cervical tourniquet) &2359.0 ml (for cervical plus infundibulopelvic ligament tourniquet)

The mean blood loss in the intervention groups was
240.70 ml lower
(359.61 ml lower to 121.79 ml lower) for the cervical tourniquet study & 1870 ml lower (2547.16 ml lower to 1192.84 ml lower) for the cervical plus infundibulopelvic ligament tourniquet study

MD ‐240.70 (‐359.61 to ‐121.79) for cervical touniquet study & ‐1870 (‐2547.16 to ‐1192.84) for the cervical plus infundibulopelvic ligament tourniquet study

121
(2 studies)

⊕⊕⊝⊝
low1

We rated down the quality of evidence (by 2) because the data were derived from two small studies that were not pooled together due to significant clinical and statistical heterogeneity.

One study used polyglactin suture round both the cervix and infundibulopelvic ligament, while the other used a Foley catheter round the cervix.

Need for blood transfusion
Participants who received blood transfusion

539 per 1000 for cervical tourniquet study &786 per 1000 for cervical plus infundibulopelvic ligament study

204 per 1000
for cervical tourniquet study &71 per 1000 for cervical plus infundibulopelvic ligament study

OR 0.22
(0.09 to 0.55) or cervical tourniquet study &

OR 0.02

(0.00 to 0.23) for cervical plus infundibulopelvic ligament study

121
(2 studies)

⊕⊕⊝⊝
low1

We rated down the quality of evidence (by 2) because the data were derived from two small studies which were not pooled together because of significant heterogeneity.

One study used polyglactin suture round both the cervix and infundibulopelvic ligament, while the other used a Foley catheter round the cervix.

Duration of surgery (min)
Operative time

The mean duration of surgery in the control groups was
118 min

The mean duration of surgery in the intervention groups was
4 min lower
(29.28 lower to 21.28 higher)

MD ‐4.00

(‐29.28 to 21.28)

28
(1 study)

⊕⊝⊝⊝
very low

We rated down the quality of evidence (by 3) because the data were derived from one small study and the effect estimate was imprecise

CI: Confidence interval; MD: mean difference; OR: Odds ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1In one trial the allocation concealment was unclear and in the other trial allocation concealment was achieved by sealed sequentially‐numbered opaque envelopes containing computer‐generated random numbers.

Figures and Tables -
Summary of findings 5. Peri‐cervical tourniquet compared to no treatment to reduce blood loss during myomectomy for fibroids
Navigate to table in Review
Summary of findings 6. Gelatin‐thrombin matrix compared to placebo or no treatment to reduce blood loss during myomectomy for fibroids

Gelatin‐thrombin matrix compared to placebo or no treatment to reduce blood loss during myomectomy for fibroids

Patient or population: Women with fibroids
Settings: University teaching hospital in Spain
Intervention: Gelatin‐thrombin matrix
Comparison: Placebo or no treatment

Outcomes

Illustrative comparative risks (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Placebo

Gelatin‐thrombin matrix

Blood loss (ml)
Estimated blood loss during myomectomy

The mean blood loss in placebo groups was
625 ml

The mean blood loss in intervention groups was
545 ml lower
(593.26 to 496.74 lower)

MD ‐545.00 (‐593.26 to ‐496.74)

50
(1 study)

⊕⊕⊝⊝
low1

We rated down the quality of evidence (by 2) because the data were derived from one small study, and it is unclear if outcome assessors were blind

Need for blood transfusion
Participants who received blood transfusion

400 per 1000

4 per 1000
(0 to 40)

OR 0.01
(0 to 0.1)

50
(1 study)

⊕⊕⊝⊝
low1

We rated down the quality of evidence (by 2) because the data were derived from one small study, it is unclear if outcome assessors were blind, and the effect estimate was imprecise

Duration of surgery (min)
Operative time

The mean duration of surgery in placebo group was
60 min

The mean duration of surgery in intervention group was
5.00 min higher
(1.29 to 8.71 higher)

MD 5.00

(1.29 to 8.71)

50
(1 study)

⊕⊕⊝⊝
low1

We rated down the quality of evidence (by 2) because the data were derived from one small study, it is unclear if outcome assessors were blind, and the effect estimate was imprecise

CI: Confidence interval;MD: Mean difference; OR: Odds ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Allocation concealment not reported.

Figures and Tables -
Summary of findings 6. Gelatin‐thrombin matrix compared to placebo or no treatment to reduce blood loss during myomectomy for fibroids
Navigate to table in Review
Summary of findings 7. Ascorbic acid compared to no treatment to reduce blood loss during myomectomy for fibroids

Ascorbic acid compared to placebo or no treatment to reduce blood loss during myomectomy for fibroids

Patient or population: Women with fibroids
Settings: Tertiary hospital in Iran
Intervention: Ascorbic acid
Comparison: No treatment

Outcomes

Illustrative comparative risks (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

No treatment

Ascorbic acid

Blood loss (ml)
Estimated blood loss during myomectomy

The mean blood loss in the control group was
932.9 ml

The mean blood loss in the intervention group was
411.46 ml lower
(502.58 to 320.34 lower)

MD ‐411.46

(‐502.58 to ‐320.34)

102
(1 study)

⊕⊕⊝⊝
low1

We rated down the quality of evidence (by 2) because the data were derived from one small study, and it is unclear how allocation concealment was done

Need for blood transfusion
Participants who received blood transfusion

180 per 1000

68 per 1000
(20 to 238)

OR 0.38
(0.11 to 1.32)

104
(1 study)

⊕⊝⊝⊝
very low1

We rated down the quality of evidence (by 2) because the data were derived from one small study, it is unclear how allocation concealment was done, and the estimate was imprecise

Duration of surgery (min)
Operative time

The mean duration of surgery in the control group was
68 min

The mean duration of surgery in the intervention group was
26.00 min lower
(33.1 to 18.9 lower)

MD ‐26.00

(‐33.10 to ‐18.90)

102
(1 study)

⊕⊕⊝⊝
low1

We rated down the quality of evidence (by 2) because the data were derived from one small study, and it is unclear how allocation concealment was done

CI: Confidence interval; MD: Mean difference; OR: Odds ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Allocation concealment not reported.

Figures and Tables -
Summary of findings 7. Ascorbic acid compared to no treatment to reduce blood loss during myomectomy for fibroids
Navigate to table in Review
Comparison 1. Misoprostol versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Blood loss (ml) Show forest plot

2

89

Mean Difference (IV, Fixed, 95% CI)

‐97.88 [‐125.52, ‐70.24]

1.1 Abdominal myomectomy

1

25

Mean Difference (IV, Fixed, 95% CI)

‐149.0 [‐229.24, ‐68.76]

1.2 Laparoscopic myomectomy

1

64

Mean Difference (IV, Fixed, 95% CI)

‐91.0 [‐120.44, ‐61.56]

2 Need for blood transfusion Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3 Duration of surgery (min) Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

3.1 Abdominal myomectomy

1

25

Mean Difference (IV, Random, 95% CI)

‐9.5 [‐15.90, ‐3.10]

3.2 Laparoscopic myomectomy

1

64

Mean Difference (IV, Random, 95% CI)

9.0 [‐1.63, 19.63]

4 Postoperative haemoglobin (g/dl) Show forest plot

2

89

Mean Difference (IV, Fixed, 95% CI)

0.69 [0.37, 1.02]

5 Duration of hospital stay (days) Show forest plot

1

25

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.82, 0.82]

6 Postoperative haemoglobin drop (g/dl) Show forest plot

1

67

Mean Difference (IV, Fixed, 95% CI)

‐0.60 [‐0.78, ‐0.42]

7 Postoperative complications Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.1 Postoperative fever

2

89

Odds Ratio (M‐H, Fixed, 95% CI)

0.94 [0.23, 3.88]
Figures and Tables -
Comparison 1. Misoprostol versus placebo
Navigate to table in Review
Comparison 2. Vasopressin versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Blood loss (ml) Show forest plot

3

128

Mean Difference (IV, Fixed, 95% CI)

‐199.97 [‐223.83, ‐176.12]

1.1 Abdominal myomectomy

1

20

Mean Difference (IV, Fixed, 95% CI)

‐450.00 [‐507.49, ‐392.51]

1.2 Laparoscopic myomectomy

2

108

Mean Difference (IV, Fixed, 95% CI)

‐147.95 [‐174.17, ‐121.73]

2 Need for blood transfusion Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 Abdominal myomectomy

1

20

Odds Ratio (M‐H, Fixed, 95% CI)

0.11 [0.01, 1.24]

2.2 Laparoscopic myomectomy

1

70

Odds Ratio (M‐H, Fixed, 95% CI)

0.18 [0.02, 1.60]

3 Duration of surgery (min) Show forest plot

2

108

Mean Difference (IV, Fixed, 95% CI)

‐27.72 [‐35.82, ‐19.61]

4 Duration of hospital stay (days) Show forest plot

2

108

Mean Difference (IV, Random, 95% CI)

0.11 [‐0.69, 0.91]

5 Postoperative complications Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 Adhesions to bowel and/or omentum

1

38

Odds Ratio (M‐H, Fixed, 95% CI)

2.02 [0.54, 7.49]

5.2 Adnexal adhesions

1

38

Odds Ratio (M‐H, Fixed, 95% CI)

1.87 [0.39, 8.93]

6 Pregnancy after myomectomy Show forest plot

1

38

Odds Ratio (M‐H, Fixed, 95% CI)

0.64 [0.18, 2.31]

7 Conversion of laparoscopy to laparotomy Show forest plot

1

70

Odds Ratio (M‐H, Fixed, 95% CI)

7.65 [0.38, 153.75]
Figures and Tables -
Comparison 2. Vasopressin versus placebo
Navigate to table in Review
Comparison 3. Bupivicaine plus epinephrine versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Blood loss (ml) Show forest plot

1

60

Mean Difference (IV, Fixed, 95% CI)

‐68.6 [‐93.69, ‐43.51]

2 Duration of surgery (min) Show forest plot

1

60

Mean Difference (IV, Fixed, 95% CI)

‐30.5 [‐37.68, ‐23.32]
Figures and Tables -
Comparison 3. Bupivicaine plus epinephrine versus placebo
Navigate to table in Review
Comparison 4. Peri‐cervical tourniquet versus no treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Blood loss (ml) Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 Blood loss ‐ cervical tourniquet (ml)

1

93

Mean Difference (IV, Fixed, 95% CI)

‐240.70 [‐359.61, ‐121.79]

1.2 Blood loss ‐ cervical & infundibulopelvic ligament tourniquet

1

28

Mean Difference (IV, Fixed, 95% CI)

‐1870.0 [‐2547.16, ‐1192.84]

2 Need for blood transfusion Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 Need for blood transfusion ‐ cervical tourniquet

1

93

Odds Ratio (M‐H, Fixed, 95% CI)

0.22 [0.09, 0.55]

2.2 Need for blood transfusion ‐ cervical & infundibulopelvic ligament tourniquet

1

28

Odds Ratio (M‐H, Fixed, 95% CI)

0.02 [0.00, 0.23]

3 Duration of surgery (min) Show forest plot

1

28

Mean Difference (IV, Fixed, 95% CI)

‐4.0 [‐29.28, 21.28]

4 Postoperative complications Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 Postoperative fever

1

93

Odds Ratio (M‐H, Fixed, 95% CI)

1.09 [0.46, 2.59]

4.2 Postoperative anaemia

1

93

Odds Ratio (M‐H, Fixed, 95% CI)

1.09 [0.46, 2.59]

4.3 Urinary tract infection

1

93

Odds Ratio (M‐H, Fixed, 95% CI)

0.71 [0.13, 3.70]

4.4 Prolonged vaginal bleeding

1

93

Odds Ratio (M‐H, Fixed, 95% CI)

2.21 [0.09, 55.82]

4.5 Pelvic abscess

1

93

Odds Ratio (M‐H, Fixed, 95% CI)

2.21 [0.09, 55.82]

4.6 Intestinal obstruction

1

93

Odds Ratio (M‐H, Fixed, 95% CI)

2.21 [0.09, 55.82]

4.7 Bladder injury

1

93

Odds Ratio (M‐H, Fixed, 95% CI)

0.24 [0.01, 5.94]
Figures and Tables -
Comparison 4. Peri‐cervical tourniquet versus no treatment
Navigate to table in Review
Comparison 5. Oxytocin versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Blood loss (ml) Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

2 Need for blood transfusion Show forest plot

2

154

Odds Ratio (M‐H, Random, 95% CI)

0.54 [0.03, 8.51]

3 Duration of surgery (min) Show forest plot

2

154

Mean Difference (IV, Fixed, 95% CI)

3.50 [‐1.88, 8.88]

4 Postoperative complications Show forest plot

1

60

Odds Ratio (M‐H, Fixed, 95% CI)

1.0 [0.06, 16.76]

5 Duration of hospital stay (days) Show forest plot

1

60

Mean Difference (IV, Fixed, 95% CI)

‐0.60 [‐1.19, ‐0.01]
Figures and Tables -
Comparison 5. Oxytocin versus placebo
Navigate to table in Review
Comparison 6. Chemical dissection with mesna versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Duration of surgery (min) Show forest plot

1

58

Mean Difference (IV, Fixed, 95% CI)

‐20.0 [‐28.64, ‐11.36]

2 Duration of hospital stay (days) Show forest plot

1

58

Mean Difference (IV, Fixed, 95% CI)

‐1.0 [‐1.12, ‐0.88]

3 Postoperative haemoglobin (g/dl) Show forest plot

1

58

Mean Difference (IV, Fixed, 95% CI)

0.5 [0.42, 0.58]

4 Postoperative haematocrit Show forest plot

1

58

Mean Difference (IV, Fixed, 95% CI)

1.90 [1.30, 2.50]

5 Postoperative complications Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 Postoperative fever

1

58

Odds Ratio (M‐H, Fixed, 95% CI)

0.14 [0.02, 1.22]
Figures and Tables -
Comparison 6. Chemical dissection with mesna versus placebo
Navigate to table in Review
Comparison 7. Myoma morcellation versus standard technique of enucleation (no treatment)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Blood loss (ml) Show forest plot

1

48

Mean Difference (IV, Fixed, 95% CI)

65.40 [‐36.47, 167.27]

2 Duration of surgery (min) Show forest plot

1

48

Mean Difference (IV, Fixed, 95% CI)

‐25.30 [‐44.23, ‐6.37]

3 Duration of hospital stay (days) Show forest plot

1

48

Mean Difference (IV, Fixed, 95% CI)

‐0.07 [‐0.18, 0.04]
Figures and Tables -
Comparison 7. Myoma morcellation versus standard technique of enucleation (no treatment)
Navigate to table in Review
Comparison 8. Intravenous injection of tranexamic acid versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Blood loss (ml) Show forest plot

1

100

Mean Difference (IV, Fixed, 95% CI)

‐243.0 [‐460.02, ‐25.98]

2 Need for blood transfusion Show forest plot

1

100

Odds Ratio (M‐H, Fixed, 95% CI)

1.71 [0.68, 4.30]

3 Duration of surgery (min) Show forest plot

1

100

Mean Difference (IV, Fixed, 95% CI)

‐11.0 [‐21.09, ‐0.91]

4 Postoperative haemoglobin (g/dl) Show forest plot

1

100

Mean Difference (IV, Fixed, 95% CI)

0.21 [‐0.36, 0.78]

5 Postoperative haematocrit Show forest plot

1

100

Mean Difference (IV, Fixed, 95% CI)

1.0 [‐0.43, 2.43]
Figures and Tables -
Comparison 8. Intravenous injection of tranexamic acid versus placebo
Navigate to table in Review
Comparison 9. Gelatin‐thrombin matrix versus placebo or no treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Blood loss (ml) Show forest plot

1

50

Mean Difference (IV, Fixed, 95% CI)

‐545.0 [‐593.26, ‐496.74]

2 Need for blood transfusion Show forest plot

1

50

Odds Ratio (M‐H, Fixed, 95% CI)

0.01 [0.00, 0.10]

3 Postoperative vaginal blood loss (ml) Show forest plot

1

50

Mean Difference (IV, Fixed, 95% CI)

‐225.0 [‐254.46, ‐195.54]

4 Duration of surgery (min) Show forest plot

1

50

Mean Difference (IV, Fixed, 95% CI)

5.0 [1.29, 8.71]

5 Postoperative haemoglobin drop (g/dl) Show forest plot

1

50

Mean Difference (IV, Fixed, 95% CI)

‐2.3 [‐2.66, ‐1.94]

6 Duration of hospital stay (days) Show forest plot

1

50

Mean Difference (IV, Fixed, 95% CI)

‐2.0 [‐2.69, ‐1.31]

7 Postoperative fever Show forest plot

1

50

Odds Ratio (M‐H, Random, 95% CI)

0.32 [0.01, 8.25]
Figures and Tables -
Comparison 9. Gelatin‐thrombin matrix versus placebo or no treatment
Navigate to table in Review
Comparison 10. Ascorbic acid versus placebo or no treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Blood loss (ml) Show forest plot

1

102

Mean Difference (IV, Fixed, 95% CI)

‐411.46 [‐502.58, ‐320.34]

2 Need for blood transfusion Show forest plot

1

102

Odds Ratio (M‐H, Fixed, 95% CI)

0.38 [0.11, 1.32]

3 Duration of surgery (min) Show forest plot

1

102

Mean Difference (IV, Fixed, 95% CI)

‐26.0 [‐33.10, ‐18.90]

4 Duration of hospital stay (days) Show forest plot

1

102

Mean Difference (IV, Fixed, 95% CI)

‐0.40 [‐0.65, ‐0.15]

5 Posoperative haemoglobin drop (g/dl) Show forest plot

1

102

Mean Difference (IV, Fixed, 95% CI)

0.14 [‐0.22, 0.50]

6 Pospoerative hematocrit drop (%) Show forest plot

1

102

Mean Difference (IV, Fixed, 95% CI)

‐0.70 [‐1.34, ‐0.06]

7 Posoperative complications Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

7.1 Postoperative fever

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

7.2 Postoperative vomiting

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

7.3 Postoperative constipation

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

7.4 Severe pain

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]
Figures and Tables -
Comparison 10. Ascorbic acid versus placebo or no treatment
Navigate to table in Review
Comparison 11. Dinoprostone versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Blood loss (ml) Show forest plot

1

108

Mean Difference (IV, Fixed, 95% CI)

‐131.60 [‐253.42, ‐9.78]

2 Need for blood transfusion Show forest plot

1

108

Odds Ratio (M‐H, Fixed, 95% CI)

0.17 [0.04, 0.81]

3 Duration of surgery (min) Show forest plot

1

108

Mean Difference (IV, Fixed, 95% CI)

‐2.60 [‐12.55, 7.35]

4 Duration of hospital stay (days) Show forest plot

1

108

Mean Difference (IV, Fixed, 95% CI)

0.30 [‐0.22, 0.82]

5 Postoperative haemoglobin (g/dl) Show forest plot

1

108

Mean Difference (IV, Fixed, 95% CI)

0.10 [‐0.39, 0.59]

6 Postoperative haemoglobin drop (g/dl) Show forest plot

1

108

Mean Difference (IV, Fixed, 95% CI)

‐0.5 [‐0.88, ‐0.12]

7 Postoperative complications Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.1 Postoperative fever

1

108

Odds Ratio (M‐H, Fixed, 95% CI)

1.53 [0.25, 9.54]
Figures and Tables -
Comparison 11. Dinoprostone versus placebo
Navigate to table in Review
Comparison 12. Loop ligation of myoma pseudocapsule plus vasopressin versus no treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Blood loss (ml) Show forest plot

1

70

Mean Difference (IV, Fixed, 95% CI)

‐305.01 [‐354.83, ‐255.19]

2 Need for blood transfusion Show forest plot

1

70

Odds Ratio (M‐H, Fixed, 95% CI)

0.08 [0.00, 1.47]

3 Duration of surgery (min) Show forest plot

1

70

Mean Difference (IV, Fixed, 95% CI)

‐32.76 [‐40.81, ‐24.71]

4 Duration of hospital stay (days) Show forest plot

1

70

Mean Difference (IV, Fixed, 95% CI)

‐1.46 [‐1.85, ‐1.07]
Figures and Tables -
Comparison 12. Loop ligation of myoma pseudocapsule plus vasopressin versus no treatment
Navigate to table in Review
Comparison 13. Temporary clipping of uterine artery versus no treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Need for blood transfusion Show forest plot

1

166

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2 Duration of surgery (min) Show forest plot

1

166

Mean Difference (IV, Fixed, 95% CI)

40.0 [30.01, 49.99]

3 Postoperative haemoglobin drop (g/dl) Show forest plot

1

166

Mean Difference (IV, Fixed, 95% CI)

‐0.25 [‐0.61, 0.11]

4 Duration of hospital stay (days) Show forest plot

1

166

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.15, 0.15]

5 Postoperative complications Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 Postoperative bleeding

1

166

Odds Ratio (M‐H, Fixed, 95% CI)

2.18 [0.19, 24.51]

5.2 Uterine hematoma

1

166

Odds Ratio (M‐H, Fixed, 95% CI)

3.31 [0.34, 32.51]

5.3 Postoperative sepsis

1

166

Odds Ratio (M‐H, Fixed, 95% CI)

3.26 [0.13, 81.29]

5.4 Bleeding from point of trocar insertion

1

166

Odds Ratio (M‐H, Fixed, 95% CI)

3.26 [0.13, 81.29]

5.5 Postoperative urinary tract infection

1

166

Odds Ratio (M‐H, Fixed, 95% CI)

3.26 [0.13, 81.29]

5.6 Trocar site hernia

1

166

Odds Ratio (M‐H, Fixed, 95% CI)

3.26 [0.13, 81.29]

5.7 Sinus venous thrombosis

1

166

Odds Ratio (M‐H, Fixed, 95% CI)

3.26 [0.13, 81.29]

5.8 Lung artery embolism

1

166

Odds Ratio (M‐H, Fixed, 95% CI)

0.35 [0.01, 8.82]

5.9 Cardiac arrhythmia

1

166

Odds Ratio (M‐H, Fixed, 95% CI)

0.35 [0.01, 8.82]
Figures and Tables -
Comparison 13. Temporary clipping of uterine artery versus no treatment
Navigate to table in Review
Comparison 14. Fibrin sealant patch versus no treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Blood loss (ml) Show forest plot

1

70

Mean Difference (IV, Fixed, 95% CI)

‐26.5 [‐44.47, ‐8.53]

2 Postoperative blood loss in drainage bag Show forest plot

1

70

Mean Difference (IV, Fixed, 95% CI)

‐44.60 [‐65.06, ‐24.14]

3 Need for blood transfusion Show forest plot

1

70

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4 Duration of surgery (min) Show forest plot

1

70

Mean Difference (IV, Fixed, 95% CI)

‐0.40 [‐4.47, 3.67]

5 Duration of hospital stay (days) Show forest plot

1

70

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.09, 0.09]

6 Conception after surgery Show forest plot

1

70

Odds Ratio (M‐H, Fixed, 95% CI)

3.16 [0.76, 13.11]
Figures and Tables -
Comparison 14. Fibrin sealant patch versus no treatment
Navigate to table in Review