Pre-treatment with GnRHa or ulipristal acetate prior to laparoscopic and laparotomic myomectomy: A systematic review and meta-analysis

Abstract

Background: Myomectomy has potential risks of complications. To reduce these risks, medical pre-treatment can be applied to reduce fibroid size and thereby potentially decrease intra-operative blood loss, the need for blood transfusion and emergency hysterectomy. The aim of this systematic review and meta-analysis is to study the effectiveness of medical pre-treatment with Gonadotropin-releasing hormone agonists (GnRHa) or ulipristal acetate prior to laparoscopic or laparotomic myomectomy on intra-operative and post-operative outcomes.

Methods: We performed an extensive search in Embase.com, Wiley/Cochrane Library and PubMed in accordance with the Prisma guidelines. All studies published as full papers in peer reviewed journals using GnRHa or ulipristal acetate as medical pre-treatment independent of route of administration or dosage before laparotomic or laparoscopic myomectomy were included. The primary outcome was duration of surgery. Secondary outcomes were duration of enucleation, blood loss, degree of difficulty of surgery, identification of cleavage planes, proportion of vertical incisions, conversion rate, frequency of blood transfusions, post-operative complications, duration of hospital stay, frequency of recurrence of fibroids, frequency of uterine adhesions, recovery time and quality of life. No language restrictions were applied. Meta-analysis were performed where possible.

Findings: Twenty-three studies were included. In laparotomic myomectomy, pre-treatment with GnRHa decreases intra-operative blood loss with 97.39ml (95% CI -111.80 to -82.97) compared to no pre-treatment or placebo. Pre-treatment with GnRHa before laparoscopic myomectomies also shows a reduction in intra-operative blood loss by 23.03ml (95% CI -40.79 to -5.27) and in the frequency of blood transfusions (OR 0.17, 95% CI 0.05 to 0.55) compared to no pre-treatment. Only two retrospective cohort studies reported on pre-treatment with ulipristal acetate compared to no pre-treatment before laparoscopic myomectomy showing a statistically significant reduction in intra-operative blood loss, duration of surgery and frequency of blood transfusions after pre-treatment with ulipristal acetate.

Conclusion: Administration of GnRHa prior to laparotomic myomectomy reduces blood loss and might decrease uterine adhesion formation. Pre-treatment with GnRHa before laparoscopic myomectomy reduces blood loss, the frequency of blood transfusions and might increase recurrence rate of fibroids, however it should be taken into account that some results are mainly based on cohort studies. Other pre-treatment agent ulipristal acetate has not been investigated sufficiently for relevant surgical outcomes.

Fig 1. PRISMA Flow diagram.

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram of study selection.

Fig 2. Overall risk of bias for included randomized controlled trials (RCT’s).

‘Risk of bias’ tool was used as described in the Cochrane Handbook. Studies were classified as low risk of bias (+), unclear risk of bias (?) or high risk of bias (-). Quality items: random sequence generation (selection bias), allocation concealment (selection bias), blinding of participants and personnel (performance bias), blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias) and power analysis and/or in-/exclusioncriteria reported (publication bias). This figure shows the overall quality of included RCT’s qualified by low risk of bias (green colored bar), unclear risk of bias (yellow colored bar) and high risk of bias (red colored bar).

Fig 3. Risk of bias summary randomized controlled trials (RCT’s).

The Cochrane Collaboration’s ‘Risk of Bias’ tool was used as described in the Cochrane Handbook. Studies were classified as low risk of bias (green circle with ‘plus’ sign), unclear risk of bias (yellow circle with ‘question mark’ sign) or high risk of bias (red circle with ‘minus’ sign).

Fig 4. Risk of bias for included cohort studies.

The ‘Strengthening the Reporting of Observational Studies in Epidemiology’ (STROBE) checklist was used to assess the risk of bias for the included cohort studies. The items checked are: setting (item 5), participants (item 6), variables (item 7), data sources/ measurements (item 8), bias (item 9), study size/ power analysis (item 10) and statistical methods (item 12). For the ‘results’ section the following items were selected: participants (item 13), descriptive data (item 14), main results (item 16). Each item was scored as low (+), moderate (±) or high (-) risk of bias.

Fig 5

Effect of GnRHa versus no pre-treatment before laparotomic (a) and laparoscopic (b) myomectomies. Forest plots for meta-analysis performed on duration of surgery.

Fig 6. Effect of GnRHa versus no pre-treatment before laparotomic myomectomies.

Forest plots for meta-analysis performed on duration of enucleation.

Fig 7

Effect of GnRHa versus no pre-treatment before laparotomic (a) and laparoscopic (b) myomectomies. Forest plots for meta-analysis performed on intra-operative blood loss.

Fig 8. Effect of GnRHa versus no pre-treatment before laparotomic myomectomies.

Forest plots for meta-analysis performed on proportion of vertical incisions.

Fig 9

Effect of GnRHa versus no pre-treatment before laparotomic (a) and laparoscopic (b) myomectomies. Forest plots for meta-analysis performed on frequency of blood transfusions.

Fig 10

Effect of GnRHa versus no pre-treatment before laparotomic (a) and laparoscopic (b) myomectomies. Forest plots for meta-analysis performed on complication rate.

Fig 11

Effect of GnRHa versus no pre-treatment before laparotomic (a) and laparoscopic (b) myomectomies. Forest plots for meta-analysis performed on duration of hospital stay.

Fig 12

Effect of GnRHa versus no pre-treatment before laparotomic (a) and laparoscopic (b) myomectomies. Forest plots for meta-analysis performed on recurrence of fibroids.

Fig 13. Effect of ulipristal acetate versus no pre-treatment before laparoscopic myomectomy.

Forest plot for meta-analysis performed on intra-operative blood loss.