Misoprostol for medical treatment of missed abortion: a systematic review and network meta-analysis

Hang-Lin Wu, Sheeba Marwah, Pei Wang, Qiu-Meng Wang, Xiao-Wen Chen, Hang-Lin Wu, Sheeba Marwah, Pei Wang, Qiu-Meng Wang, Xiao-Wen Chen

Abstract

The efficacy and safety of misoprostol alone for missed abortion varied with different regimens. To evaluate existing evidence for the medical management of missed abortion using misoprostol, we undertook a comprehensive review and meta-analysis. The electronic literature search was conducted using PubMed, the Cochrane Library, Embase, EBSCOhost Online Research Databases, Springer Link, ScienceDirect, Web of Science, Ovid Medline and Google Scholar. 18 studies of 1802 participants were included in our analysis. Compared with vaginal misoprostol of 800 ug or sublingual misoprostol of 600 ug, lower-dose regimens (200 ug or 400 ug) by any route of administration tend to be significantly less effective in producing abortion within about 24 hours. In terms of efficacy, the most effective treatment was sublingual misoprostol of 600 ug and the least effective was oral misoprostol of 400 ug. In terms of tolerability, vaginal misoprostol of 400 ug was reported with fewer side effects and sublingual misoprostol of 600 ug was reported with more side effects. Misoprostol is a non-invasive, effective medical method for completion of abortion in missed abortion. Sublingual misoprostol of 600 ug or vaginal misoprostol of 800 ug may be a good choice for the first dose. The ideal dose and medication interval of misoprostol however needs to be further researched.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Article retrieval and screening.
Figure 2
Figure 2
Network diagram of all studies and studies included in analyses of complete abortion rate within about 24 hours and main side effects. (A) Studies comparing different routes of misoprostol. (B) Studies comparing different routes or doses of misoprostol. (C) Complete abortion rate within about 24 hours. (D) Main side effects totally. Studies are classified according to the first dose of misoprostol in both groups; The width of the lines is proportional to the number of trials directly comparing each pair of interventions; The size of each node is proportional to the number of trails comparing a single intervention totally. Interventions are sequenced as follows: A. Oral 400 ug; B. Oral 800 ug; C. Sublingual 400 ug; D. Sublingual 600 ug; E. Sublingual 800 ug; F. Vaginal 200 ug; G. Vaginal 400 ug; H. Vaginal 600 ug; I. Vaginal 800 ug.
Figure 3
Figure 3
Network meta-analysis of complete abortion rate within about 24 hours and main side effects. Interventions are sequenced as follows: A. Oral 400 ug; C. Sublingual 400 ug; D. Sublingual 600 ug; E. Sublingual 800 ug; F. Vaginal 200 ug; G. Vaginal 400 ug; H. Vaginal 600 ug; I. Vaginal 800 ug.
Figure 4
Figure 4
Ranking of all the interventions in network meta-analysis. Information of ranking is located at the intersection of the column-defining outcome and the row-defining intervention; The number in the first row is the ranking of all the interventions; The first number below in brackets is the surface under the cumulative ranking curve (SUCRA) while the second is the probability of the intervention to be the best.

References

    1. Wood SL, Brian PH. Medical management of missed abortion: a randomized clinical trial. Obstet Gynecol. 2002;99:563–566.
    1. Joint study of Royal College of general practitioner and Royal College of obstetrician and gynaecologist. Induced abortion operations and their early sequelae. J R Coll Gen Pract. 35, 175–180 (1985).
    1. Chia KV, Ogbo VI. Medical termination of missed abortion. J Obstet Gynaecol. 2002;22:184–186. doi: 10.1080/01443610120113382.
    1. Petrou S, Trinder J, Brocklehurst P, Smith L. Economic evaluation of alternative management methods of first-trimester miscarriage based on results from the MIST trial. BJOG. 2006;113:879–889. doi: 10.1111/j.1471-0528.2006.00998.x.
    1. Jukovic D, Ross JA, Nicoladies KH. Expectant management of missed miscarriage. Br J Obstet Gynaecol. 1998;105:670–671. doi: 10.1111/j.1471-0528.1998.tb10184.x.
    1. Neilsen S, Hahlin M. Expectant management of first-trimester spontaneous abortion. Lancet. 1995;345:84–86. doi: 10.1016/S0140-6736(95)90060-8.
    1. Luise C, et al. Outcome of expectant management of spontaneous first trimester miscarriage: observational study. BMJ. 2002;324:873–875. doi: 10.1136/bmj.324.7342.873.
    1. Huchon C, et al. Pregnancy loss: French clinical practice guidelines. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2016;201:18–26. doi: 10.1016/j.ejogrb.2016.02.015.
    1. Anderson J, et al. A randomised controlled trial of oral versus vaginal misoprostol for medical management of early fetal demise. International Journal of Gynecology and Obstetrics. 2009;107:S533–S533. doi: 10.1016/S0020-7292(09)61912-3.
    1. Kushwah DS, Kushwah B, Salman MT, Verma VK. Acceptability and safety profile of oral and sublingual misoprostol for uterine evacuation following early fetal demise. Indian J Pharmacol. 2011;43:306–310. doi: 10.4103/0253-7613.81513.
    1. Leladier C, et al. Mifepristone (RU 486) induces embryo expulsion in first trimester non-developing pregnancies: a prospective randomised trial. Hum Reprod. 1993;8:492–495. doi: 10.1093/oxfordjournals.humrep.a138078.
    1. Gronlund A, et al. Management of missed abortion: comparison of medical treatment with either mifepristone misoprostol or misoprostol alone with surgical evacuation. A multi-center trial in Copenhagen county, Denmark. Acta Obstet Gynecol Scand. 2002;81:1060–1065. doi: 10.1034/j.1600-0412.2002.811111.x.
    1. Nielsen S, Hahlin M, Platz-Christensen JJ. Unsuccessful treatment of missed abortion with a combination of an antiprogesterone and a prostaglandine E1 analogue. Br J Obstet Gynaecol. 1997;104:1094–1096. doi: 10.1111/j.1471-0528.1997.tb12075.x.
    1. Tasnee S, Gul MS, Navid S, Alam K. Efficacy and safety of misoprostolin missed miscarriage in terms of blood loss. Rawal Medical Journal. 2014;39:314–318.
    1. Seyam YS, Flamerzi MA, Abdallah MM, Ahmed B. Vaginal misoprostol in the management of first trimester non-viable pregnancy. Qatar Medical Journal. 2007;17:14–19.
    1. Poveda C, et al. Intrauterine misoprostol: a new high effective treatment of missed abortion. Fertility and Sterility. 2001;76:S96. doi: 10.1016/S0015-0282(01)02284-1.
    1. Sharma D, Singhal SR, Rani XX. Sublingual misoprostol in management of missed abortion in India. Trop Doct. 2007;37:39–40. doi: 10.1258/004947507779952023.
    1. EI-Sokkary HH. Comparison Between Sublingual and Vaginal Administration of Misoprostol in Management of Missed Abortion. J Obstet Gynaecol India. 2016;66:24–29. doi: 10.1007/s13224-015-0757-y.
    1. Haberal A, Celikkanat H, Batioglu S. Oral misoprostol use in early complicated pregnancy. Adv Contracept. 1996;12:139–143. doi: 10.1007/BF01849635.
    1. National Institute for Health and Care Excellence guidelines. Ectopic pregnancy and miscarriage: diagnosis and initial management. (2012).
    1. Prasartsakulchai C, Tannirandorn Y. A comparison of vaginal misoprostol 800 microg versus 400 microg in early pregnancy failure: a randomized controlled trial. J Med Assoc Thai. 2004;87:S18–23.
    1. Seervi N, et al. Comparison of different regimes of misoprostol for the termination of early pregnancy failure. Medical Journal Armed Forces India. 2014;70:360–363. doi: 10.1016/j.mjafi.2014.08.012.
    1. Shah N, Azam SI, Khan NH. Sublingual versus vaginal misoprostol in the management of missed miscarriage. J Pak Med Assoc. 2010;60:113–116.
    1. Marwah S, et al. A Comparative Study to Evaluate the Efficacy of Vaginal vs Oral Prostaglandin E1 Analogue (Misoprostol) in Management of First Trimester Missed Abortion. J Clin Diagn Res. 2016;10:Qc14–18.
    1. Akanksha L, Ramanjeet K, Priya S. A study to compare the clinical outcome of sublingual and vaginal misoprostol in the medical management. Int J Reprod Contracept Obstet Gynecol. 2016;5:491–494.
    1. Tanha FD, Feizi M, Shariat M. Sublingual versus vaginal misoprostol for the management of missed abortion. J Obstet Gynaecol Res. 2010;36:525–532. doi: 10.1111/j.1447-0756.2010.01229.x.
    1. Rita GS, Kumar S. A randomised comparison of oral and vaginal misoprostol for medical management of first trimester missed abortion. JK Science. 2006;8:35–38.
    1. Ayudhaya OP, Herabutya Y, Chanrachakul B, Ayuthaya NI. O-Prasertsawat,P. A comparison of the efficacy of sublingual and oral misoprostol 400 microgram in the management of early pregnancy failure: a randomized controlled trial. J Med Assoc Thai. 2006;89(Suppl 4):S5–10.
    1. Hombalegowda RB, Samapthkumar S, Vana H, Jogi P, Ramaiah R. A randomized controlled trial comparing different doses of intravaginal misoprostol for early pregnancy failure. Contraception. 2015;92:364–365. doi: 10.1016/j.contraception.2015.06.051.
    1. Srikhao N, Tannirandorn Y. A comparison of vaginal misoprostol 800 microg versus 400 microg for anembryonic pregnancy: a randomized comparative trial. J Med Assoc Thai. 2005;88(Suppl 2):S41–47.
    1. Kovavisarach E, Jamnansiri C. Intravaginal misoprostol 600 microg and 800 microg for the treatment of early pregnancy failure. Int J Gynaecol Obstet. 2005;90:208–212. doi: 10.1016/j.ijgo.2005.04.016.
    1. Suchonwanit P. Comparative study between vaginal misoprostol 200 mg and 400 mg in first trimester intrauterine fetal death and anembryonic gestation. Thai Journal of Obstetrics and Gynaecology. 1999;11:263.
    1. Tang OS, Schweer H, Seyberth HW, Lee SW, Ho PC. Pharmacokinetics of different routes of administration of misoprostol. Hum Reprod. 2002;17:332–336. doi: 10.1093/humrep/17.2.332.
    1. Pongsatha S, Tongsong T. Randomized comparison of dry tablet insertion versus gel form of vaginal misoprostol for second trimester pregnancy termination. J Obstet Gynaecol Res. 2008;34:199–203. doi: 10.1111/j.1447-0756.2008.00757.x.
    1. Saichua C, Phupong V. A randomized controlled trial comparing powdery sublingual misoprostol and sublingual misoprostol tablet for management of embryonic death or anembryonic pregnancy. Arch Gynecol Obstet. 2009;280:431–435. doi: 10.1007/s00404-009-0947-x.
    1. Bhattacharjee N, et al. A randomized comparative study on vaginal administration of acetic acid-moistened versus dry misoprostol for mid-trimester pregnancy termination. Arch Gynecol Obstet. 2012;285:311–316. doi: 10.1007/s00404-011-1949-z.
    1. Pongsatha S, Tongsong T. Randomized controlled study comparing misoprostol moistened with normal saline and with acetic acid for second-trimester pregnancy termination. Is it different? J Obstet Gynaecol Res. 2011;37:882–886. doi: 10.1111/j.1447-0756.2010.01458.x.
    1. Creinin MD, Carbonell JL, Schwartz JL, Varela L, Tanda R. A randomized trial of the effect of moistening misoprostol before vaginal administration when used with methotrexate for abortion. Contraception. 1999;59:11–16. doi: 10.1016/S0010-7824(98)00142-5.
    1. Jain JK, Mishell DR. A comparison of misoprostol with and without laminaria tents for induction of second-trimester abortion. Am J Obstet Gynecol. 1996;175:173–177. doi: 10.1016/S0002-9378(96)70270-3.
    1. Jmylyan M, Hydry M. Comparison of the Efficacy of Castor Oil and Vaginal Misoprostol With Vaginal Misopostol Alone for Treatment of Missed Abortion. Arak Medical University Journal. 2015;18:30–38.
    1. Areerat S, Teerapat C. Comparison of sublingual and vaginal misoprostol for termination of early pregnancy failure. Thai J Obstet Gynaecol. 2014;22:128–136.
    1. Mohammed, S. Oral versus vaginal misoprostol for termination of frist trimester missed abortion. MSc for Cairo University. eses/thesis/view/13990 (2013).
    1. Ngoc NT, Blum J, Westheimer E, Quan TT, Winikoff B. Medical treatment of missed abortion using misoprostol. Int J Gynaecol Obstet. 2004;87:138–142. doi: 10.1016/j.ijgo.2004.07.015.
    1. Tang OS, Lau WN, Ng EH, Lee SW, Ho PC. A prospective randomized repeated doses of vaginal study to compare the use of with sublingual misoprostol in the management of first trimester silent miscarriages. Hum Reprod. 2013;18:176–81. doi: 10.1093/humrep/deg013.
    1. Tang OS, et al. A randomized trial to compare the use of sublingual misoprostol with or without an additional 1 week course for the management of first trimester silent miscarriage. Hum Reprod. 2006;21:189–92. doi: 10.1093/humrep/dei303.
    1. Higgins, J. G. S. Cochrane Handbook for Systematic reviews of Interventions (v5.1.0). (2011).
    1. Caldwell DM, Ades AE, Higgins JP. Simultaneous comparison of multiple treatments: combining direct and indirect evidence. BMJ. 2005;331:897–900. doi: 10.1136/bmj.331.7521.897.
    1. Dias S, Ades A, Sutton A, Welton N. Evidence synthesis for decision making 2: a generalized linear modeling framework for pairwise and network meta-analysis of randomized controlled trials. Med Decis Making. 2013;33:607–617. doi: 10.1177/0272989X12458724.
    1. Salanti G, Ades AE, Ioannidis JP. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol. 2011;64:163–171. doi: 10.1016/j.jclinepi.2010.03.016.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren