Skip to main content
SpringerLink
Log in

Preoperative Misoprostol to Reduce Blood Loss and Related Morbidities During Abdominal Hysterectomy: a Systematic Review and Meta-analysis of 10 Randomized Placebo-Controlled Trials

  • Review
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

The objective of this study is to perform a meta-analysis of all randomized controlled trials (RCTs) that surveyed the efficacy and safety of preoperative misoprostol versus placebo during abdominal hysterectomy. Six databases were screened from inception until 3 August 2022. The eligible studies were assessed for risk of bias. The outcomes were summarized as mean difference (MD) and risk ratio (RR) with 95% confidence intervals (CI) in a random-effects model. Ten RCTs with 1076 patients (misoprostol = 537, placebo = 539 patients) were analyzed. Six and four RCTs had an overall low and high risk of bias (single-blinded), respectively. The mean intraoperative blood loss (n = 10 RCTs, MD =  − 78.97 ml, 95% [− 130.89, − 27.06], p = 0.003), mean difference in hemoglobin drop (n = 10 RCTs, MD =  − 0.42 g/dl, 95% CI [− 0.69, − 0.14], p = 0.003), and mean length of hospital stay (n = 5 RCTs, MD =  − 0.2 d, 95% CI [− 0.24, − 0.16], p < 0.001) were significantly reduced in favor of the misoprostol group compared with the placebo group. However, there were no significant differences between both groups regarding the mean operative time (n = 8 RCTs, MD =  − 0.63 min, 95% CI [− 5.07, 3.81], p = 0.78), rate of perioperative blood transfusion (n = 7 RCTs, RR = 0.83, 95% CI [0.53, 1.3], p = 0.42), and rate of drug-related adverse events (i.e., nausea, vomiting, diarrhea, headache, chills, and fever). Leave-one-out sensitivity analyses revealed stability for all endpoints, except hospitalization stay. There was no publication bias for all endpoints, except perioperative blood transfusion. Among patients undergoing abdominal hysterectomy, preoperative administration of misoprostol was largely safe and linked to substantial decrease in blood loss-related morbidities.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data Availability

All data are available within the manuscript and its supplemental files.

Code Availability

Review Manager Software version 5.4.0. for Windows.

References

  1. Bachmann GA. Hysterectomy. A critical review. J Reprod Med. 1990;35(9):839–62.

    CAS  PubMed  Google Scholar 

  2. Johnson N, Barlow D, Lethaby A, Tavender E, Curr L, Garry R. Methods of hysterectomy: systematic review and meta-analysis of randomised controlled trials. BMJ. 2005;330(7506):1478.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Hill DJ. Complications of hysterectomy. Baillieres Clin Obstet Gynaecol. 1997;11(1):181–97.

    Article  CAS  PubMed  Google Scholar 

  4. Clarke-Pearson DL, Geller EJ. Complications of hysterectomy. Obstet Gynecol. 2013;121(3):654–73.

    Article  PubMed  Google Scholar 

  5. Ramdhan RC, Loukas M, Tubbs RS. Anatomical complications of hysterectomy: a review. Clin Anat. 2017;30(7):946–52.

    Article  PubMed  Google Scholar 

  6. Tang OS, Gemzell-Danielsson K, Ho PC. Misoprostol: pharmacokinetic profiles, effects on the uterus and side-effects. Int J Gynaecol Obstet. 2007;99(Suppl 2):S160–7.

    Article  CAS  PubMed  Google Scholar 

  7. Choksuchat C. Clinical use of misoprostol in nonpregnant women: review article. J Minim Invasive Gynecol. 2010;17(4):449–55.

    Article  PubMed  Google Scholar 

  8. Chai J, Hon E, Li CF, Pun TC, Yeung SB, Ho PC. A pilot study of pre-operative misoprostol in reducing operative blood loss during hysterectomy. Eur J Obstet Gynecol Reprod Biol. 2011;158(1):72–5.

    Article  CAS  PubMed  Google Scholar 

  9. Panichpongpan A, Satirapod C, Likittanasombat P, Ayuttaya NIN. Preoperative sublingual misoprostol in reducing intraoperative blood loss during abdominal hysterectomy. Thai J Obstet Gynaecol 2014:187–93.

  10. Biswas J, Chaudhuri P, Mandal A, Bandyopadhyay SN, Dasgupta S, Pal A. Effect of a single preoperative dose of sublingual misoprostol on intraoperative blood loss during total abdominal hysterectomy. Int J Gynaecol Obstet. 2013;122(3):244–7.

    Article  CAS  PubMed  Google Scholar 

  11. Tabatabai A, Karimi-Zarchi M, Meibodi B, Vaghefi M, Yazdian P, Zeidabadi M, et al. Effects of a single rectal dose of Misoprostol prior to abdominal hysterectomy in women with symptomatic leiomyoma: a randomized double blind clinical trial. Electron Physician. 2015;7(6):1372.

    PubMed  PubMed Central  Google Scholar 

  12. Nankali A, Fakheri T, Hematti M, Noori T. Pre-operative sublingual misoprostol and intra-operative blood loss during total abdominal hysterectomy: a randomized single-blinded controlled clinical trial. Middle East J Fam Med. 2017;7(10):35.

    Article  Google Scholar 

  13. Makled A, Alsaied A, Ismail O, Farhan S. Effect of sublingual misoprostol on intraoperative blood loss during abdominal hysterectomy: randomized controlled trial. Egypt J Hosp Med. 2017;69(1):1692–7.

    Article  Google Scholar 

  14. Anant M, Agarwal A, Sinha K, Raj N. Single-dose preoperative vaginal misoprostol for reducing blood loss during abdominal hysterectomy: a randomized study. J Gynecol Surg. 2021;37(5):424–9.

    Article  Google Scholar 

  15. Harinsalai T, Meckjarusnapa M, Rattanakosol J, Sripipattanakul M, Tangsiriwatthana T. The effectiveness of sublingual misoprostol in reducing operative blood loss during total abdominal hysterectomy: a randomized controlled trial. Thai J Obstet Gynaecol 2019:210–5.

  16. Parashi S, Astaraei V, Vahdat M, Dini P, Mohammadianamiri M. The Effect of a Single Preoperative dose of sublingual misoprostol in reducing intraoperative blood loss after total abdominal hysterectomy: a single-blind randomized controlled trial. J Obstet, Gynecol Cancer Res (JOGCR). 2018;3(4):143–7.

    Google Scholar 

  17. Aziz AEA, Sokary AASE, Borg HMES, Marey SK. Effect of preoperative single dose misoprostol on intraoperative blood loss during abdominal hysterectomy: a randomized controlled trial. J Adv Med Med Res. 2022;34(1):127–34.

    Article  Google Scholar 

  18. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7): e1000097.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Higgins J GS, editors. Cochrane handbook for systematic reviews of interventions version 5.1.0 [Internet]. [updated March 2011]. The Cochrane Collaboration, www.handbook.cochrane.org AAf.

  20. Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343: d5928.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, et al. Grading quality of evidence and strength of recommendations. BMJ. 2004;328(7454):1490.

    Article  PubMed  Google Scholar 

  22. Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135.

    Article  PubMed  PubMed Central  Google Scholar 

  23. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88.

    Article  CAS  PubMed  Google Scholar 

  24. Dickersin K, Berlin JA. Meta-analysis: state-of-the-science. Epidemiol Rev. 1992;14:154–76.

    Article  CAS  PubMed  Google Scholar 

  25. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Thompson JD, Birch HW. Indications of hysterectomy. Clin Obstet Gynecol. 1981;24(4):1245–58.

    Article  CAS  PubMed  Google Scholar 

  28. Discepola F, Valenti DA, Reinhold C, Tulandi T. Analysis of arterial blood vessels surrounding the myoma: relevance to myomectomy. Obstet Gynecol. 2007;110(6):1301–3.

    Article  PubMed  Google Scholar 

  29. Chen CL, Xu YJ, Liu P, Zhu JH, Ma B, Zeng BL, et al. Characteristics of vascular supply to uterine leiomyoma: an analysis of digital subtraction angiography imaging in 518 cases. Eur Radiol. 2013;23(3):774–9.

    Article  PubMed  Google Scholar 

  30. Maged AM, Wali AA, Metwally AA, Salah N. The efficacy of misoprostol in reducing intraoperative blood loss in women undergoing elective cesarean section. A systematic review and meta-analysis. J Obstet Gynaecol Res. 2022;48(8):2038–70.

  31. Wali S, Balfoussia D, Touqmatchi D, Quinn S. Misoprostol for open myomectomy: a systematic review and meta-analysis of randomised control trials. BJOG. 2021;128(3):476–83.

    Article  CAS  PubMed  Google Scholar 

  32. Murji A, Lam M, Allen B, Richard L, Shariff SZ, Austin PC, et al. Risks of preoperative anemia in women undergoing elective hysterectomy and myomectomy. Am J Obstet Gynecol. 2019;221(6):629.e1-e18.

    Article  PubMed  Google Scholar 

  33. Rock WA Jr, Meeks GR. Managing anemia and blood loss in elective gynecologic surgery patients. J Reprod Med. 2001;46(5 Suppl):507–14.

    PubMed  Google Scholar 

  34. Abu-Zaid A, Baradwan S, Badghish E, AlSghan R, Ghazi A, Albouq B, et al. Prophylactic tranexamic acid to reduce blood loss and related morbidities during hysterectomy: a systematic review and meta-analysis of randomized controlled trials. Obstet Gynecol Sci. 2022;65(5):406–19.

  35. Tang J, Kapp N, Dragoman M, de Souza JP. WHO recommendations for misoprostol use for obstetric and gynecologic indications. Int J Gynaecol Obstet. 2013;121(2):186–9.

    Article  CAS  PubMed  Google Scholar 

  36. Gingold JA, Chichura A, Harnegie MP, Kho RM. Perioperative interventions to minimize blood loss at the time of hysterectomy for uterine leiomyomas: a systematic review and meta-analysis. J Minim Invasive Gynecol. 2019;26(7):1234-52.e1.

    Article  PubMed  Google Scholar 

  37. Park H, Yoon BS, Seong SJ, Kim JY, Shim JY, Park CT. Can misoprostol reduce blood loss in laparoscopy-assisted vaginal hysterectomy? Aust N Z J Obstet Gynaecol. 2011;51(3):248–51.

    Article  PubMed  Google Scholar 

  38. Hafidh B, Latifah HM, Gari A, Alshahrani MS, AlSghan R, Alkhamis WH, et al. Vasopressin to control blood loss during hysterectomy: a systematic review and meta-analysis of randomized controlled trials. J Minim Invasive Gynecol 2021.

  39. Lethaby A, Vollenhoven B, Sowter M. Efficacy of pre-operative gonadotrophin hormone releasing analogues for women with uterine fibroids undergoing hysterectomy or myomectomy: a systematic review. BJOG. 2002;109(10):1097–108.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

    Ahmed Abu-Zaid

  2. Department of Pharmacology, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, TN, 38163, USA

    Ahmed Abu-Zaid

  3. Faculty of Medicine, Assiut University, Assiut, Egypt

    Yasmine Adel Mohammed & Reem Sayad

  4. Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia

    Saeed Baradwan

  5. Faculty of Medicine, Cairo University, Cairo, Egypt

    Esraa Faraag & Eman Reda Mohammed

  6. Faculty of Medicine, Sohag University, Sohag, Egypt

    Suhaila Mamdouh Mohammed

  7. Department of Obstetrics and Gynecology, Cairo University, Cairo, Egypt

    Ahmed Samy Ashour

Authors
  1. Ahmed Abu-Zaid
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasmine Adel Mohammed
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Saeed Baradwan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Reem Sayad
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Esraa Faraag
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eman Reda Mohammed
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Suhaila Mamdouh Mohammed
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ahmed Samy Ashour
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AA contributed to study conception, data analysis, study supervision, and manuscript writing. YAM, SB, RS, EF, ERM, SMM, and ASA contributed to literature review, data collection, data interpretation, and revision of manuscript for editorial and intellectual contents. All authors read and approved the final draft of manuscript.

Corresponding author

Correspondence to Ahmed Abu-Zaid.

Ethics declarations

Ethics Approval

Not required as this research does not involve direct patient or animal contact.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Conflict of Interest

The authors declare no competing interests.

IRB Approval

Not applicable. IRB approval is not needed as this research (systematic review and meta-analysis) does not involve direct patient or animal contact.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 20 KB)

Supplementary file2 (DOCX 120 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abu-Zaid, A., Mohammed, Y.A., Baradwan, S. et al. Preoperative Misoprostol to Reduce Blood Loss and Related Morbidities During Abdominal Hysterectomy: a Systematic Review and Meta-analysis of 10 Randomized Placebo-Controlled Trials. Reprod. Sci. 30, 1470–1481 (2023). https://doi.org/10.1007/s43032-022-01121-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-022-01121-8

Keywords

Search

Navigation