The use of misoprostol for cervical priming prior to hysteroscopy: a systematic review and analysis

Figures & data

Figure 1 Flow diagram and quality of the selected study.

Notes: (A) Flow diagram for study selection. (B) Risk of bias assessment. (C) Funnel plot of comparison: need for cervical dilatation.
Abbreviations: D&C, dilatation and curettage; RCTs, randomized controlled trials; RR, risk ratio; SE, standard error.

Table 1 Main characteristics of the included RCT studies

Study (year)	Country	Participants (females)	Setting (operative/diagnostic)	Dose (μg)	Route of administration	Outcomes
Atay et al^Citation11 (1997)	Turkey	Patients undergoing hysteroscopy	Diagnostic + operative	400	Vaginal	Number of patients with adequate cervical ripening (7 mm hysteroscopic sheath or 6 mm Hegar fits), dilatation time, dilatation pain score (in comparison with menstrual pain), cervical bleeding, cervical laceration, uterine perforation (while introducing hysteroscopic sheath)
Preutthipan and Herabutya^Citation12 (1999)	Thailand	Nonpregnant females before hysteroscopy	Diagnostic + operative	200	Vaginal	Cervical width, duration of hysteroscopy, need for cervical dilatation, cervical tear, side effects (mild lower abdominal pain, slight vaginal bleeding, nausea, watery diarrhea, perceived increase in body temperature)
Preutthipan and Herabutya^Citation13 (2000)	Thailand	Nulliparous females	Operative	200	Vaginal	Cervical width, need for cervical dilatation, time for cervical dilatation to Hegar 9, duration of operative hysteroscopy, complications (cervical tear, creation of a false track, uterine perforation)
Ngai et al^Citation16 (2001)	Hong Kong	Postmenopausal females	Diagnostic	400	Oral	Cervical dilatation, cumulative force, duration of operation, blood loss, side effects (nausea, dizziness, fatigue, lower abdominal pain, vaginal bleeding, vomiting, diarrhea)
Fung et al^Citation17 (2002)	Hong Kong	Postmenopausal females	Diagnostic	800	Vaginal	Extra needed dilatation, cervical width, operative time, operative complications (cervical tear, uterine perforation), side effects (lower abdominal pain, fever, diarrhea)
Thomas et al^Citation14 (2002)	Canada	Patients undergoing hysteroscopy	Operative	800	Oral	Time required for dilatation, ease of dilatation, no complications, cervical lacerations perforation, side effects (nausea, bleeding, diarrhea, cramps)
Bisharah et al^Citation8 (2003)	Canada	Nulliparous females	Operative	100	Sublingual	Baseline cervical diameter, degree of difficulty to dilate, time to dilate to 9 mm, side effects and complications of the procedure (cervical tear, uterine perforation, creation of false passage, bleeding, mild abdominal cramps)
Fernandez et al^Citation9 (2004)	France	Premenopausal females	Operative	200/400/800	Vaginal	Cervical width, subjective ease of cervical dilatation, the time required for dilatation up to Hegar No 10, preoperative pain, complications (perforation, cervical laceration, false track)
Barcaite et al^Citation15 (2005)	Lithuania	Perimenopausal + postmenopausal females	Diagnostic + operative	400	Vaginal	Number of females who needed extra cervical dilatation, cervical width (no Hegar), operative time, complications, side effects (abdominal pain)
Healey et al^Citation18 (2007)	Canada	Premenopausal females	Diagnostic	400	Oral	Need to further dilate the cervix, preprocedural dilatation, time required to further dilate cervix, postprocedural dilatation, side effects (nausea, vomiting, diarrhea, abdominal pain, menstrual cramps, vaginal bleeding, vaginal spotting, headache)
Da Costa et al^Citation23 (2008)	Brazil	Postmenopausal females	Diagnostic	200	Vaginal	The need for additional cervical dilation, degree of pain during procedure, procedure duration, side effects (genital bleeding, nausea, vomiting, diarrhea, hyperthermia), complications (uterine perforation, false passages, cervical lacerations, and infections)
Uckuyu et al^Citation21 (2008)	Turkey	Females who have undergone cesarean section and no vaginal deliveries	Operative	400	Vaginal	Cervical width, complication (uterine perforation, false passages, bleeding cervical lacerations), failure rates
Valente et al^Citation24 (2008)	Brazil	Females of reproductive age	Diagnostic	400	Vaginal	Pain, side effects (bleeding, nausea, vomiting, diarrhea, fever), complications (uterine perforation, creation of a false cervical passage, cervical laceration, infection, cramping, genital discharge)
Waddell et al^Citation25 (2008)	Canada	Postmenopausal and premenopausal females aged 18 years or older	Diagnostic	400	Vaginal	Force needed to dilate cervix, pain-related measurements, complications (vaginal bleeding, cervical laceration, uterine perforation), side effects (nausea, diarrhea, headache, pelvic cramp, fever, or shivering)
Singh et al^Citation26 (2009)	India	Females undergoing hysteroscopy	Diagnostic	400	Vaginal	The need for cervical dilatation, a pain score on a visual analog scale of 0–10, side effects (nausea, vomiting, diarrhea, increase in body temperature, lower abdominal pain, or vaginal bleeding)
Oppegaard et al^Citation10 (2008)	Norway	Premenopausal and postmenopausal females	Operative	1,000	Vaginal	Cervical dilatation, number of females achieving cervical dilatation >5 mm, difficult dilatation, dilatation time, exposure to capsules, frequency of complications, side effects (bleeding, shivering, diarrhea, nausea, vaginal discharge)
Oppegaard et al^Citation22 (2010)	Norway	Postmenopausal females	Operative	1,000	Vaginal	Cervical dilatation at hysteroscopy, difference in dilatation at recruitment and before hysteroscopy, number of patients achieving cervical dilatation >5 mm, difficult dilatation, exposure to capsules, frequency of preoperative complications, complications within 14 days after hysteroscopy, no adverse effects, lower abdominal pain, mean level of reported preoperative pain, constipation, vaginal bleeding, vaginal discharge
Mulayim et al^Citation27 (2010)	Turkey	Premenopausal females	Diagnostic	200	Sublingual	Need for cervical dilatation, time required for dilatation, ease of dilatation, complications (cervical tear, uterine perforation, cervical suture)
El-Mazny and Abou-Salem^Citation28 (2011)	Egypt	Females in the reproductive age	Diagnostic	200	Vaginal	Ease of cervical entry, procedural time, patient acceptability, pain scoring, side effects (nausea, vomiting, abdominal pain, diarrhea, fever, shivering)
Sordia-Hernández et al^Citation30 (2011)	Mexico	Infertile females	Diagnostic	600/400	Oral/vaginal	Pain score on a visual analog scale of 0–10, surgical time, side effects (nausea, diarrhea, and abdominal pain)
Mathlouthi et al^Citation29 (2011)	Tunisia	Premenopausal and postmenopausal females	Diagnostic	200	Sublingual	Need for cervical dilatation, cervical width, complications (cervical tear, creation of false cervical track, uterine perforation, bleeding), side effects (nausea, diarrhea, and abdominal pain)
Kant et al^Citation33 (2011)	India	Postmenopausal females	Diagnostic + operative	200	Vaginal	Preprocedural cervical width, number needed for requiring additional dilatation, the time required for dilatation
Shawky Moiety and Azzam^Citation34 (2012)	Egypt	Premenopausal females	Diagnostic + operative	400/400	Sublingual/rectal	Ease of cervical dilatation, baseline cervical width, duration of cervical dilatation up to Hegar 6, cervical lacerations, complications (pain [cramps], bleeding, vomiting, diarrhea, pyrexia)
Kalampokas et al^Citation31 (2012)	Greece	Females who have only undergone cesarean section	Diagnostic	200	Vaginal	Cervical width, complications (cervical tear, creation of false cervical track, bleeding)
Bastu et al^Citation32 (2013)	Turkey	Patients with infertility	Diagnostic	200/400	Vaginal	Ease of cervical entry, baseline cervical width, pain scoring, procedural time

Abbreviation: RCT, randomized controlled trial.

Figure 2 Comparison of the need for cervical dilatation between the misoprostol group and the placebo or no medication group, including both operative and diagnostic hysteroscopy studies.

Notes: (A) Irrespective of the route of misoprostol administration. (B) Vaginal misoprostol administration.
Abbreviations: CI, confidence interval; df, degrees of freedom; M–H, Mantel–Haenszel.

Figure 3 Comparison of the need for cervical dilatation between the misoprostol group and the placebo or no medication group, including vaginal, oral, sublingual administration routes.

Notes: (A) Operative hysteroscopy. (B) Diagnostic hysteroscopy.
Abbreviations: CI, confidence interval; df, degrees of freedom; M–H, Mantel–Haenszel.

Figure 4 Comparison of the need for cervical dilatation between the misoprostol group and the placebo or no medication group.

Notes: (A) Sublingual misoprostol administration. (B) Oral misoprostol administration.
Abbreviations: CI, confidence interval; df, degrees of freedom; M–H, Mantel–Haenszel.

Figure 5 Comparison of the cervical width prior to hysteroscopy between the misoprostol group and the placebo or no medication group.

Notes: (A) Irrespective of the route of misoprostol administration. (B) Vaginal misoprostol administration.
Abbreviations: CI, confidence interval; df, degrees of freedom; IV, independent variable; SD, standard deviation.

Figure 6 Comparison of the cervical width prior to hysteroscopy between the misoprostol group and the placebo or no medication group.

Notes: (A) Sublingual misoprostol administration. (B) Oral misoprostol administration.
Abbreviations: CI, confidence interval; df, degrees of freedom; IV, independent variable; SD, standard deviation.

Figure 7 Comparison of the cervical width prior to hysteroscopy between the misoprostol group and the placebo or no medication group.

Notes: Vaginal administration of misoprostol (A) 200 μg and (B) 400 μg.
Abbreviations: CI, confidence interval; df, degrees of freedom; IV, independent variable; SD, standard deviation.

Figure 8 Comparison of the cervical width prior to hysteroscopy between the misoprostol group and the placebo or no medication group.

Notes: Vaginal misoprostol administration (A) 800 μg and (B) 1,000 μg.
Abbreviations: CI, confidence interval; df, degrees of freedom; IV, independent variable; SD, standard deviation.

Table 2 Effect estimates on complications of hysteroscopy and side effects of misoprostol

Complication	Studies (number of participants)	Relative risk or mean difference (95% CI)	P-value
1.1 Cervical tear	14 (1,358)	0.46 (0.30, 0.73)	0.0008
1.2 Uterine perforation	9 (885)	0.67 (0.29, 1.53)	0.34
1.3 False passage	7 (628)	0.33 (0.15, 0.74)	0.007
2.1 Mild abdominal pain	14 (1,423)	5.49 (3.76, 8.00)	<0.00001
2.2 Bleeding	11 (1,150)	6.97 (3.95, 12.29)	<0.00001
2.3 Nausea	12 (1,164)	2.26 (1.42, 3.61)	0.0006
2.4 Diarrhea	11 (1,256)	6.53 (3.23, 13.22)	<0.00001
2.5 Fever	7 (786)	6.36 (2.23, 18.13)	0.0005

Note: 1, complications of hysteroscopy; 2, side effects of misoprostol.

Abbreviation: CI, confidence interval.

Figure 9 The complication of hysteroscopy: cervical laceration in the misoprostol group compared to the placebo or no medication group.

Notes: (A) Vaginal misoprostol administration. (B) Sublingual and oral misoprostol administration.
Abbreviations: CI, confidence interval; df, degrees of freedom; M–H, Mantel–Haenszel.

Figure 10 The complication of hysteroscopy: false passage in the misoprostol group compared to the placebo or no medication group.

Notes: (A) Vaginal misoprostol administration. (B) Sublingual and oral misoprostol administration.
Abbreviations: CI, confidence interval; df, degrees of freedom; M–H, Mantel–Haenszel.

AtayVDuruNKPabuccuRErgünATokacGAydinBAVaginal misoprostol for cervical dilatation before operative office hysteroscopyGynaecol Endosc1997614749

 Google Scholar

PreutthipanSHerabutyaYA randomized controlled trial of vaginal misoprostol for cervical priming before hysteroscopyObstet Gynecol199994342743010472872

 PubMed Web of Science ®Google Scholar

PreutthipanSHerabutyaYVaginal misoprostol for cervical priming before operative hysteroscopy: a randomized controlled trialObstet Gynecol200096689089411084173

 PubMed Web of Science ®Google Scholar

NgaiSWChanYMHoPCThe use of misoprostol prior to hysteroscopy in postmenopausal womenHum Reprod20011671486148811425834

 PubMed Web of Science ®Google Scholar

FungTMLamMHWongSFHoLCA randomized placebo-controlled trial of vaginal misoprostol for cervical priming before hysteroscopy in postmenopausal womenBJOG2002109556156512066947

 PubMed Web of Science ®Google Scholar

ThomasJALeylandNDurandNWindrimRCThe use of oral misoprostol as a cervical ripening agent in operative hysteroscopy: a double-blind, placebo-controlled trialAm J Obstet Gynecol2002186587687912015500

 PubMed Web of Science ®Google Scholar

BisharahMAl-FozanHTulandiTA randomized trial of sublingual misoprostol for cervical priming before hysteroscopyJ Am Assoc Gynecol Laparosc200310339039114567819

 PubMedGoogle Scholar

FernandezHAlbyJDTournouxCVaginal misoprostol for cervical ripening before operative hysteroscopy in pre-menopausal women: a double-blind, placebo-controlled trial with three dose regimensHum Reprod20041971618162115155607

 PubMed Web of Science ®Google Scholar

BarcaiteEBartuseviciusARailaiteDRNadisauskieneRVaginal misoprostol for cervical priming before hysteroscopy in perimenopausal and postmenopausal womenInt J Gynaecol Obstet200591214114516102766

 PubMed Web of Science ®Google Scholar

HealeySButlerBKumFNDunneJHutchensDCraneJMA randomized trial of oral misoprostol in premenopausal women before hysteroscopyJ Obstet Gynaecol Can200729864865217714618

 PubMedGoogle Scholar

Da CostaARPinto-NetoAMAmorimMPaivaLHScavuzziASchettiniJUse of misoprostol prior to hysteroscopy in postmenopausal women: a randomized, placebo-controlled clinical trialJ Minim Invasive Gynecol2008151677318262147

 PubMed Web of Science ®Google Scholar

UckuyuAOzcimenEESevincFCZeynelogluHBEfficacy of vaginal misoprostol before hysteroscopy for cervical priming in patients who have undergone cesarean section and no vaginal deliveriesJ Minim Invasive Gynecol200815447247518588848

 PubMed Web of Science ®Google Scholar

ValenteEPde AmorimMMCostaAAde MirandaDVVaginal misoprostol prior to diagnostic hysteroscopy in patients of reproductive age: a randomized clinical trialJ Minim Invasive Gynecol200815445245818539093

 PubMed Web of Science ®Google Scholar

WaddellGDesindesSTakserLBeaucheminMCBessettePCervical ripening using vaginal misoprostol before hysteroscopy: a double-blind randomized trialJ Minim Invasive Gynecol200815673974418971139

 PubMed Web of Science ®Google Scholar

SinghNGhoshBNahaMMittalSVaginal misoprostol for cervical priming prior to diagnostic hysteroscopy – efficacy, safety and patient satisfaction: a randomized controlled trialArch Gynecol Obstet20092791374018449549

 PubMed Web of Science ®Google Scholar

OppegaardKSNesheimBIIstreOQvigstadEComparison of self-administered vaginal misoprostol versus placebo for cervical ripening prior to operative hysteroscopy using a sequential trial designBJOG20081155663e1e918201279

 PubMed Web of Science ®Google Scholar

OppegaardKSLiengMBergAIstreOQvigstadENesheimBIA combination of misoprostol and estradiol for preoperative cervical ripening in postmenopausal women: a randomized controlled trialBJOG20101171536120002369

 PubMed Web of Science ®Google Scholar

MulayimBCelikNYOnalanGBagisTZeynelogluHBSublingual misoprostol for cervical ripening before diagnostic hysteroscopy in premenopausal women: a randomized, double blind, placebo-controlled trialFertil Steril20109372400240419243750

 PubMed Web of Science ®Google Scholar

El-MaznyAAbou-SalemNA double-blind randomized controlled trial of vaginal misoprostol for cervical priming before outpatient hysteroscopyFertil Steril201196496296521575939

 PubMed Web of Science ®Google Scholar

Sordia-HernándezLHRosales-TristanEVazquez-MendezJEffectiveness of misoprostol for office hysteroscopy without anesthesia in infertile patientsFertil Steril201195275976120728083

 PubMed Web of Science ®Google Scholar

MathlouthiNSaodiOBen TemimeRMakhloufTAttiaLChachiaASublingual misoprostol for cervical ripening before diagnostic hysteroscopy: a randomized and prospective study about 108 casesTunis Med2011891182582922179917

 PubMedGoogle Scholar

KantADivyakumarPriyambadaUA randomized trial of vaginal misoprostol for cervical priming before hysteroscopy in postmenopausal womenJ Midlife Health201121252721897735

 PubMedGoogle Scholar

Shawky MoietyFMAzzamAProstaglandins prior to hysteroscopyGynecol Surg201291169173

 Google Scholar

KalampokasESofoudisCAntonogeorgosGA randomized controlled trial for cervical priming using vaginal misoprostol prior to hysteroscopy in women who have only undergone cesarean sectionArch Gynecol Obstet2012286485385722592929

 PubMed Web of Science ®Google Scholar

BastuECelikCNehirADoganMYukselBErgunBCervical priming before diagnostic operative hysteroscopy in infertile women: a randomized, double-blind, controlled comparison of 2 vaginal misoprostol dosesInt Surg201398214014423701149

 PubMed Web of Science ®Google Scholar