Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

Kim, 2017

PS., study characteristics and results are extracted from the SR (unless stated otherwise)

SR and meta-analysis of RCTs

Literature search up to May 2016

A: Bique, 2007

B: Blohm, 2005

C: Chigbu, 2012

D: Dabash, 2010

E: Dao, 2007

F: Ganguly, 2010

G: Montesinos, 2011

H: Moodliar, 2005

I:Patua, 2013

J: Sahin, 2001

K: Shelley, 2005

L: Shochet, 2012

M: Shwekerela 2007

N:Taylor, 2011

O: Trinder, 2006

P: Weeks, 2005

Q: Zhang, 2005

Study design: RCT

Source of funding and conflicts of interest:

[commercial / non-commercial / industrial co-authorship]

‘authors reports no conflicts of interest’

 “no external sources of support supplied.’

Inclusion criteria SR:

Studies: only included randomised controlled trials (RCTs).

Types of participants

Participants were women being treated for spontaneous miscarriage

(pregnancy loss at less than 24 weeks), either where there was

ultrasound evidence of retained tissue (incomplete miscarriage) or

where the diagnosis had beenmade on clinical grounds alone, and

where there would be uncertainty whether the miscarriage was

complete or incomplete. In communities in which termination

of pregnancy was illegal or unavailable, this could have included

women who had undergone unsafe abortion.

Interventions

Trials were considered trials if they compared medical treatment of incomplete

miscarriage with other methods (e.g. expectant management,

placebo, or any other intervention including surgical evacuation,

either curettage or vacuum aspiration).

comparisons between different routes of administration of drugs

(e.g. oral versus vaginal), or between different drugs or doses of

drug, or duration or timing of treatment, if data existed.

Exclusion criteria SR:

Types of studies

quasi-RCTs and cross-over trials, conference proceedings and abstracts.

Participants:

-women with non-viable pregnancies (i.e. where the

embryo or fetus had died in utero, but in whom miscarriage had

not yet occurred) as they are covered

-studies on induced abortion of a live fetus and

for fetal anomaly

17 studies included

Important patient characteristics at baseline:

N: I/C

A:123/124

B: 64/62

C: 160/160

D: 349/348

E: 233/227

F: 77/37

G: 122/120

H: 47/47

I: 50/50

J: 40/40

K: 12/12/15

L: 480/380

M:150/150

N:113/116

O: 90/92/92

P: 160/152

Q: 30/9

Describe intervention:

A: oral misoprostol, 600 ug single-dose

B: vaginal misoprostol 400 ug; 2 tablets of 200 ug, each self-administered at home

C: Misoprostol 600 mcg orally

D: misoprostol, 400 mcg sublingually

E: oral misoprostol, 600 ug, single-dose

F: vaginal misoprostol, 800 mcg on day 1, second dose of 800 mcg on day 3, if incomplete expulsion

G: oral misoprostol, 600 ug

H: vaginal misoprostol, 600 ug (plus a second dose 24 hours later if miscarriage still not complete)

I: Misoprostol 400 mcg vaginal every 3 hours x 3 doses regardless of POC expulsion

J: oral + vaginal misoprostol

200 ug 4 times daily after application of 200 ug intravaginal misoprostol for 5 days

K: Intervention 1: vaginal misoprostol, 400u g with repeat dose 4-6 hours later if needed (= 400 ug or 800 ug) Intervention 2: surgical management, Aspiration curettage or D&C under GA

L: sublingual misoprostol, Misoprostol 400 mcg sublingual x 1 dose

M:oral misoprostol, 600 ug single-dose

N: oral misoprostol, 600 mcg

O: Intervention 1: vaginal misoprostol, 800 ug

Intervention 2: surgery, Suction curettage

P: oral misoprostol 600 ug

Q: vaginal misoprostol 800 ug (4 x 200 ug)

Describe control:

A: surgery, MVA

B: placebo

C: Surgery, MVA

D: Surgery, MVA

E: Surgery, MVA

F: Surgery, MVA

G: Surgery, MVA

H: surgery, surgical ERPC by sharp curettage following 20 U of oxytocin per litre of normal saline under GA with no prophylactic antibiotics but oral analgesics were prescribed

I: surgical: traditional suction and curettage under deep sedation with 50 mg pethidine Injection

J: surgical management Curettage, sometimes with general anaesthesia

K: expectant care

L: surgical evacuation

per standard practice of each hospital (MVA or D&C)

M: surgery, MVA

N: surgery, MVA

O: expectant care

P: surgery MVA

Q: surgery Vacuum aspiration

End-point of follow-up:

A: 1 wk

B: 1 wk

C: 2 wk

D: -

E: 1 wk

F: -

G: -

H: -

I:-

J: 10 days

K: 8 wk

L: 2 wk

M: 1 wk

N: 1 wk

O: 8 wk

P: 1 wk

Q: 8 days

For how many participants were no complete outcome data available?

(intervention/control)

A: • 23 women were excluded after randomisation because of a problem identified with the randomisation process

as discussed by authors.

• 35 women did not return at 1 week: 12 from misoprostol group and 23 from MVA group. • 10 women in misoprostol group had MVA prior to the 1 week follow-up time. These were included in the misoprostol group.

• Not strictly speaking ITT analysis, but outcomes on the 23 women excluded were reported and similar to those

included. Analysis was done on 212 women on whom data were available.

B: There was no loss to follow-up and women received their appropriate allocation. The

analysis appears to be ITT

C: no loss to follow-up reported

D: 2/697 women lost to follow-up.

E: • Lost after randomisation and before prescription: 10 in misoprostol group and 3 in the MVA group • Exclusion after randomisation: 5 in the misoprostol group and 1 in the MVA group

F: No loss to follow-up.

G: 39/242 (16.1%) women did not return for assessment and were not included in analyses

H: No loss of participants nor exclusions reported.

I: 4 lost from the intervention group – 1 woman was detected having pre-existing

jaundice. Another 1 left the hospital without intimation. 2 refused to continue treatment

following administration of the first dose of misoprostol and urged for surgical

clearance. All 4 of them were excluded from the study

J: No losses and no exclusions were reported, but nothing is described. As there is no

deviation from protocol it is assumed that analysis was by ITT

K: One woman randomised to medical prescription

(misoprostol) withdrew following randomisation and was not included in the

analyses. Medical group: 1womanwas lost to follow-up

at 10 to 14 days; 1 woman was lost to follow-up at 8 weeks

Surgical group: 1woman was lost to follow-up at 8 weeks.

Expectant group: 1 woman was lost to follow- up at 8 weeks.

L: 15 in intervention and 6 in MVA group - no information on whether this group Is

different

M: No loss to follow-up and no deviations from protocol allocation reported. ITT

analysis

N: 11/229 women lost to follow-up.

O: Loss of participants to follow-up:

• loss immediately after

randomisation: misoprostol = 0; surgery = 1; expectant care = 1.

• loss at 14-day outcomes; misoprostol = 9 ; surgery = 8; expectant care = 5.

• loss at 8-week outcomes: misoprostol = 3; surgery = 2; expectant care = 6.

Exclusions after randomisation: In each

of the surgical group and expectant care group, one woman with a viable pregnancy was excluded. Analysis was by ITT

P: Loss of participants to follow-up from 317 women randomised was considerable and was discussed by authors. Many women in the rural communities of Uganda did not come for follow-up after discharge.

• At 6 days - no loss to follow-up.

• At 1-2 weeks: Misop had 53/160 (33%) lost to follow-up - leaving 107 women.

• MVA had 70/157 (45%) lost to follow-up - leaving 82 women. 5 women were excluded in the MVA group

(3 for self-discharge and 2 women were incorrectly

excluded by the recruiter after randomisation but before treatment, 1 because

she did not fit the entry criteria and 1 because

nomanual vacuum aspiration kit was available)

• One woman in misoprostol group and 7 in MVA group were given the wrong prescription, but were included on ITT for analysis.

• Included in MVA were 6 women for whom MVA was not possible (5 amount of retained products too great and 1 the os had closed). The study was analysed by ITT based on available data.

Q: One woman lost to follow-up in the surgical group.

Medical vs expectant

Complete miscarriage (vaginal misoprostol)

Studies n=2, patients n=150, Risk Ratio (M-H, Random, 95% CI) 1.23 [0.72, 2.10]

Unplanned surgical intervention (vaginal misoprostol)

Studies n=2, patients n=308, Risk Ratio (M-H, Random, 95% CI) 0.62 [0.17, 2.26]

Pelvic infection < 14 days (vaginal misoprostol)

Studies n= 3, patients n=333, Risk Ratio (M-H, Random, 95% CI) 2.42 [0.59, 9.98]

Medical vs surgical

Complete miscarriage

Studies n=15, patients n=3862 Risk Ratio (M-H, Random, 95% CI) 0.96 [0.94, 0.98]

Unplanned surgical intervention

Studies n=11, patients n=2690 Risk Ratio (M-H, Random, 95% CI) 5.03 [2.71, 9.35]

Pelvic infection < 14 days

Studies n=7, patients n=907 Risk Ratio (M-H, Random, 95% CI) 0.70 [0.25, 1.99]

Cervical damage (Oral misoprostol)

Studies n=1, patients n=189 Risk Ratio (M-H, Random, 95% CI) 0.07 [0.00, 1.25]

Women’s views/acceptability of method

Studies n=9, patients n=3349 Risk Ratio (M-H, Random, 95% CI) 1.00 [0.99, 1.00]

Women’s views/satisfaction - continuous data (vaginal misoprostol)

Studies n=2, patients n=131 Std. Mean Difference (IV, Random, 95% CI) 1.01 [0.01, 2.00]

Nausea

Studies n=11, patients n=3015 Risk Ratio (M-H, Random, 95% CI) 2.50 [1.53, 4.09]

Vomiting

Studies n=10, patients n=2977 Risk Ratio (M-H, Random, 95% CI) 1.97 [1.36, 2.85]

Diarrhoea

Studies n=4, patients n=757 Risk Ratio (M-H, Random, 95% CI) 4.82 [1.09, 21.32]

Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Lemmers, 2017a

Type of study: Observational Cohort Misorest study

Setting and country: Multicentre, The Netherlands

Funding and conflict of interest:

funded by ZonMw, a Dutch organization for Health Research and Development

Inclusion criteria

-women with a

first trimester miscarriage treated with misoprostol

- incomplete evacuation of

the uterus at routine ultrasound scanning 1-2 wk

after initial misoprostol treatment.

Exclusion criteria

-age <18 years,

-severe vaginal bleeding or severe abdominal pain requiringimmediate intervention,

-fever (>38⁰C) requiring antibiotic

treatment and curettage,

-contraindications for curettage or a failed misoprostol-induced miscarriage as substantiated by the finding on ultrasound scanning of an intact gestational sac still being present.

N total at baseline

Curettage: n = 65

Expectant: n = 132

Important prognostic factors

Age in years, mean (SD)

Curettage: 31.4 (4.8)

Expectant: 32.7 (4.6)

Nulliparous, n (%)

Curettage: 34 (52.3)

Expectant: 65 (49.2)

Comparable at baseline?

Yes, except for median AP diameter of uterine contents Curettage: 18 mm

Expectant: 15 mm

(difference 3 mm, p = 0.04).

Curettage

Women who preferred curettage were scheduled for this procedure within 3 workdays. Curettage was performed according to local hospital protocol. Curettage could be performed as a vacuum aspiration or by blunt or sharp curettage and anesthesia was either general, regional or local.

 Expectant

Length of follow-up:

3 months

Loss-to-follow-up:

Of the 292 non-randomized eligible women 84 women

refused any study participation, three women withdrew their

consent before any data were obtained; two women who chose

expectant management, and one women who chose curettage.

One woman who underwent expectant management was lost to

follow-up.

Two women who underwent a curettage were excluded,

one had never been treated with misoprostol but had a primary

curettage for non-vital pregnancy, while the other woman still had a gestational sac in situ after misoprostol treatment.

Since having a

gestational sac present after misoprostol treatment was an

exclusion criterium, this woman was wrongfully included and therefore not considered in the analysis.

Success rate treatment

A successful outcome was defined as the finding of an empty uterus (total endometrial diameter of <10 mm) on ultrasound scan, at six weeks follow up, or an uneventful clinical course during three months of follow-up without complications or the need for (re)interventions.

Curretage: 95% (62/65)

Expectant: 85% (112/132) (RR 1.1, 95% CI 1.03-1.2).

(ORadjusted 3.4; 95% CI 0.9–12.9)

Complication rates

Curretage: 6.2%

Expectant: 2.3%

(RR 2.7, 95% CI 0.6–12).

Secondary outcomes

need for antibiotic treatment,
excessive blood loss (estimated or measured _500cc and/or blood transfusion needed)

type and number of (re)interventions ((re-)curettage, hysteroscopy, laparoscopy and laparotomy).

Reinterventions

Curettage: n=11

(n=2 curettage, n=7 hysteroscopy, n=2 curettage + hysteroscopy)

Expectant: n=24

(n= 12 curettage, n=7 hysteroscopy, n= 5 curettage + hysteroscopy)

Cohort Misorest study

Incomplete evacuation was

defined as evidence of intra-uterine remnants or an anterio-posterior (AP) diameter of the uterine cavity exceeding 10 mm in ultrasound scanning.

Lemmers, 2017b

Type of study:

Observational

Setting and country:

Multicentre, The Netherlands

Funding and conflicts of interest:

funded by ZonMw, a Dutch organization for Health Research and Development

N total at baseline

Curettage N = 95

Expectant N = 161

Curettage

Women who were allocated to/ preferred curettage were scheduled for this procedure within 3 workdays. Curettage was performed according to local hospital protocol. Curettage could be performed as a vacuum aspiration or by blunt or sharp curettage and anesthesia was either general, regional or local.

Expectant

Length of follow-up:

2.5–4.5 years

Incomplete outcome data:

Response rate

Total: 211/256 (82%)

Curettage: 76/95 (80%)

Expectant: 35/161 (84%)

P=0.49

Fertility outcomes

In 198 women pursuing a

new pregnancy:

conception rates

Curettage: 92% (67/73)

Expectant: 96% (120/125)

OR 0.96, 95% CI 0.89;1.03,

p = 0.34

ongoing pregnancy rates

Curettage: 87% (58/67) Expectant: 78% (94/120)

OR 1.12, 95% CI 0.99;1.28,

p = 0.226.

RCT + Cohort data Misorest study

Lemmers, 2016

Type of study:

open label randomized controlled trial (RCT)

Setting and country:

multicenter

in 27 hospitals within the Dutch consortium for research on women’s health, Netherlands.

Funding and conflicts of interest:

This study was funded by ZonMw, a Dutch organization for Health

Research and Development Conflict of interest: None declared.

Inclusion criteria:

-Women with a first trimester miscarriage who had been treated with misoprostol

and showing incomplete evacuation of the uterus at routine sonography

one to 2 weeks after initial misoprostol treatment were eligible for the study.

-Incomplete evacuation was defined as sonographic evidence of intrauterine

remnants or an anterio–posterior (AP) diameter of the uterine cavity exceeding 10mm.

Exclusion criteria:

-age <18 years,

-severe vaginal

bleeding or severe abdominal pain requiring immediate intervention,

-fever (>38°C) requiring antibiotic treatment and curettage,

-contraindications for

curettage or a failed misoprostol-induced miscarriage as substantiated by the sonographic finding of an intact gestational sac still being present.

N total at baseline

Curettage n=30

Expectant: n=29

RCT

Curettage

(n = 30)

Expectant

(n = 29)

Important prognostic factors

Age in years, mean (SD)

31.8 (6.5)

32.1 (4.9)

Nulliparous, n (%) 16 (53.3)

10 (34.5)

Groups comparable at baseline.

Curettage

Women allocated to curettage were scheduled for this procedure within

three work days after randomization. Curettage was performed according

to local hospital protocol, and could consist of a vacuum aspiration blunt

curettage or sharp curettage. The procedure was performed in a daycare

setting under general, regional or local anaesthesia.

Expectant

Women allocated to expectant management received no further treatment.

They were instructed to contact the hospital in case of excessive pain or blood loss, or fever.

Length of follow up:

3 months

Loss-to-follow-up:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Incomplete outcome data:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Efficacy (empty uterus at 6 weeks and/or uneventful clinical course for 3 months), n (%)

Curettage: 29 (97%)

Expectant: 22 (76%)

RR (95%CI): 1.27 (1.03–1.58)

Complications

I: 3 (10.0)

C: 3 (10.3)

1.0 (0.85–1.19)

Bleeding ≥500cc, n (%)

I: 0 (0.0)

C: 2 (6.9)

N/A

Antibiotic treatment, n (%)

I: 1 (3.3)

C: 1 (3.4)

0.97 (0.1–14.7)

Asherman syndrome, n (%)

I: 1 (3.3)

C: 0 (0.0)

N/A

Post-spinal headache, n (%)

I: 1 (3.3)

C: 0 (0.0)

N/A

Bleeding, days (median, IQR) I: 7 (3–14)

C: 14 (2–42)

P = 0.08

Pain, days (median, IQR)

I: 1 (0–2)

C: 7.5 (0.8–18.8)

P = 0.048

(Re)interventions

(Re)curettage, n (%)

I: 0 (0)

C: 4 (13.8)

N/A

Hysteroscopy, n (%)

I: 2 (6.7)

C: 3 (10.3)

0.64 (0.1–3.6)

Due to a strong patient preference, mainly for expectant management, the targeted sample size could not be included and the trial was stopped prematurely.

Shokry, 2014

Type of study:

Observational

Setting and country:

Private practice with a University affiliation, Egypt

Conflicts of interest:

‘none’

Inclusion criteria:

-Pregnant women between 8 and 12 week cases requesting medical management for spontaneous first trimester incomplete abortion.

Exclusion criteria:

-hemodynamically unstable, -septic abortion,

-fever,

-bronchial asthma

-known hypersensitivity to misoprostol

N total at baseline:

Misoprostol: n=60

ERPC: n=60

Important prognostic factors²:

Age (years)

26.9 ±4.6

27.1± 5.4

Gestational age (weeks)

8.4 ±1.3

8.2±1.2

Parity, Primiparous {No. (%)]

11 (20.4%)

12 (23.5%)

History of previous abortion {No. (%)}

8 (14.8%)

6 (11.8%)

Groups comparable at baseline.

Misoprostol

The eligible patients were divided into two groups according to patients’ choice; group (I) received

misoprostol tablet 400 mcg (Cytotec, Serono) every 4 h for a maximum of three doses

Surgical (ERPC)

group (II) did not receive any uterotonics and directly underwent vaginal surgical evacuation under general anesthesia by the standard technique of the hospital.

Length of follow-up:

1 wk

Loss-to-follow-up:

Intervention:

N (%) = 6

Reasons (describe)

Not described

Control:

N (%) = 9

Reasons (describe)

Not described

Incomplete outcome data:

Intervention:

-

Control:

-

Success of the treatment method {No. (%)}

Miso: 43 (79.6%)

ERPC: 51 (100%)

P= 0.0006

Patient method satisfaction {No. (%)}

Miso: 46 (85.2%)

ERPC: 47 (92.2%)

P= 0.2617

Side effects

Incidence of side effects, {No. (%)}

Miso: 11 (20.4%)

ERPC: 6 (11.8%)

P= 0.2315

Pain

Incidence of significant lower abdominal cramps (within 7 days) VAS (0-10) score >4 {No. (%)}

Miso: 5 (9.3%)

ERPC: 3 (5.9%)

P= 0.5144

The diagnosis of incomplete abortion was confirmed by

transvaginal ultrasonography examination using a Sono

ACE 9900 Prime Multi-beam 3-D Ultrasound System (Medison, Korea) check for the presence or absence of retained products of conception

Al-Ma’ani, 2014

Type of study:

RCT

Setting and country:

Germany

Funding and conflicts of interest:

‘We declare that we have no conflict of interest.’

Inclusion criteria:

-women with missed miscarriage including blighted ovum

- women with incomplete miscarriage,

- in good health

-aged 16 years or older,

-gestational age of B13 weeks,

-with anterior–posterior diameter of retained products ranging between 15 and 50 mm,

-bleeding not excessive with normal packed cell volume,

-haemodynamically stable and not febrile.

Exclusion criteria:

-Women with complete miscarriage

N total at baseline:

N=234

Surgical: n=125

Expectant: n=109

Incomplete miscarriage, N=93

Surgical: n=51

Expectant: n=42

Surgical

Women in the surgical management group were scheduled for surgical uterine evacuation under general anaesthesia within a week after inclusion in the study.

Expectant

Expectant management group were informed that they might have some bleeding and pain and they were recommended

to use Paracetamol tablets (non-proprietary) for

the pain. If the woman experienced heavy bleeding, or severe pain or developed an offensive smelling vaginal discharge, she was advised to return to the hospital for surgical uterine evacuation.

Length of follow-up:

4 wk

Loss-to-follow-up:

Intervention:

N (%) 10

Reasons (describe)

Not described

Control:

N (%) 7

Reasons (describe)

Not described

Incomplete outcome data:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Succesrate

Group incomplete miscarriage

Expectant, n=42 (Perc total 41.2 %)

Succesrate: n=38 (90.5 %)

Surgical n= 51 (perc total 44.3 %)

Succesrate n= 50 (98 %)

Outcomes missed + incomplete

Expectant (n = 102)

Surgical (n = 115)

Success rate at 4 weeks

Exp: 83 (81.4 %)

Surg: 110 (95.7 %)

P= 0.0029

Emergency curettage

Exp: 5 (4.9 %)

Surg: 6 (5.2 %)

P=0.1744

Second curettage

Exp: 4 (3.9 %)

Surg: 5 (4.3 %)

P=0.0975

Duration of bleeding (days)

Exp: 11 (2.3)

Surg: 7 (2.1)

P= 0.0001

Change in PCV at 4 weeks Exp: -1.60 (3.3)

Surg: -1.51 (1.4)

P=0.7899

Duration of pain (days) Exp: 8.1 (2.7)

Surg: 5.5 (1.7)

P= 0.0001

Requirement of analgesia Exp: 25 (24.5 %)

Surg: 16 (13.9 %)

0.6711

Complications (total)

Exp: 6 (5.9 %)

Surg: 7 (6.1 %)

P=0.2479

Pelvic infection

Exp: 2 (1.9 %)

Surg: 4 (3.5 %)

P= 0.0146

Bleeding

Exp: 4 (3.9 %)

Surg: 2 (1.7 %)

P= 0.0199

Uterine perforation

Exp: 0

Surg: 1 (0.9 %)

NS

Nadarajah, 2014

Type of study:

RCT

Setting and country:

Malaysia

Funding and conflicts of interest:

Not reported

Inclusion criteria:

Women with a pregnancy loss at _14 weeks of gestation who

had been diagnosed with either a missed or an incomplete miscarriage.

Womenwho presented at 6–14 weeks of amenorrhoea (based on the last menstrual period (LMP)) with vaginal bleeding, abdominal pain or suspected missed, incomplete or threatened miscarriage were screened prior to recruitment.

Exclusion criteria:

1. Under 18 years old.

2. Inability to understand informed consent form.

3. Factors (severe per vaginal bleeding, hemodynamically unstable, abdominal pain or fever >37.5 8C) necessitating immediate surgical evacuation.

4. Septic miscarriage.

5. Current anticoagulation, or abnormal clotting profile or full blood count.

6. Ectopic pregnancy or pregnancy of unknown location (PUL).

7. High risk patients (immunocompromised, haematological disorders,

severe asthma, heart disease, etc.).

N total at baseline:

Intervention: surgical management (n = 180)

Control: expectant

management (n = 180)

Incomplete

Intervention : surgical management n=72

Control: expectant management n=80

Important prognostic factors²:

Total group randomised

Surg 180

Exp 180

Age

I: 29.11 (6.01)

C: 28.72 (5.58)

Parity

Mean (SD)

I: 1.76 (1.59)

C: 1.79 (1.57)

Gestational age (days)

Mean (SD)

I: 73.17 (13.80)

C: 75.13 (13.56)

Groups comparable at baseline.

Surgical

In the group assigned to surgical intervention, evacuation was done electively by suction curettage within 3 days of randomisation.

The procedure was performed in the operating theatre under general anaesthesia and aseptic precautions. Routine prophylactic antibiotic was not used during the procedure.

All uncomplicated cases were discharged 6 h after the procedure.

Expectant

Women assigned to expectant management were followed up every 2 weeks for a total duration of 6 weeks. Transvaginal ultrasound (TVS) was performed to measure the endometrial thickness (ET) in women who had passed POC. The amount of

bleeding was subjectively assessed using the pictorial chart and objectively quantified by the haemoglobin (Hb) levels, measured during the first visit and subsequently following surgical evacuation or after the patient passed POC. In the event of complaints

such as excessive vaginal bleeding, foul smelling discharge or fever,

or if the patient requested surgical intervention, surgical evacuation

was carried out. By the end of 6 weeks, if the ET was >15 mm or gestational sac remained intact, the patient was advised to have

surgical intervention.

Length of follow-up:

6 wk

Loss-to-follow-up:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Incomplete outcome data:

Intervention:

N (%) 5

Reasons (describe)

Control:

N (%) 0

Reasons (describe)

Succesrate

Surgical (n = 175)

Expectant (n = 177)

Incomplete

Surgical

Yes 64 (89%)

No 8 (11%)

Missing 2

Total 72

P= 0.378

Expectant

Yes 63 (79%)

No 17 (21%)

Missing 1

Total 80

P= 0.312

Each miscarriage was classified as missed or incomplete.

The ultrasound criteria for missed miscarriage were according to guidelines from the Royal College of Obstetricians and

Gynaecologists (RCOG):

1. A mean gestational sac diameter of >20 mm without a measurable embryonic pole.

2. An embryo with crown rump length of >6 mm without cardiac activity.

3. Crown rump lump length of <6 mm with no changes at a repeat scan performed 7 days later.

4. A gestational sac diameter of <15 mm, not showing growth after a 7-day interval.

Ultrasound criteria for the diagnosis of incomplete miscarriage were:

1. Central cavity echoes(s).

2. Thick irregular echoes in the uterine cavity.

3. Echo consistent with intrauterine tissues or clots.

4. Endometrial line not present and the cavity is filled with echogenic products of conception.

5. Endometrial thickness >15 mm.

Dangalla, 2012

Type of study:

RCT

Setting and country:

University Unit of Teaching

Hospital,

Sri Lanka

Funding and conflicts of interest:

Inclusion criteria:

-women with uncomplicated spontaneous incomplete miscarriage

 -presenting within three

days of bleeding

- <14 weeks POA,

-RPC 15-50 mm

Exclusion criteria:

-Women who refused randomisation because of strong preference for either form of management

-significant vaginal bleeding, pain or fever,

-evidence or suspicion of induced abortion,

-other medical conditions which necessitated

early ERPC

-history of cervical OS

incompetence

N total at baseline:

N=80

N=80

Important prognostic factors:

Age – years:

mean (95% CI)

Exp 29.0 (27.7 - 30.3)

ERPC 28.9 (27.7 - 30.1)

Groups comparable at baseline.

Surgical (ERPC)

Women allocated to the ERPC group had ERPC and blunt curettage of endometrial cavity under general anaesthesia within 24 hours of ultrasound evaluation and discharged home after an overnight stay following ERPC.

Expectant

Women allocated to the expectant care group were

discharged home after an overnight stay.

Length of follow-up:

4 wk

Loss-to-follow-up:

Intervention:

N (%) 6

Reasons (describe)

Control:

N (%) 4

Reasons (describe)

Incomplete outcome data:

Intervention:

-

Control:

-

RPC Expelled:

1 week

C: 55 (69%)

I: 79 (98.8%)

<0.001

2 weeks

C: 67 (84%)

I: 80 (100%)

<0.001

4 weeks

C: 77 (96.6%)

I: 80 (100%)

NS

Required ERPC

C: n=3

I: n=1

NS

Infection

C: n=2

I: n=3

NS

Uterine perforation

C: n=0

I: n=2

NS

Needed blood transfusion

C: n=1

I: n=0

NS

Headache and nausea

C: n=0

I: n=2

NS

Satisfied with management 78 (97.5%)

78 (97.5%)

NS

Patients who had RPC more than 50 mm in the AP diameter were offered ERPC

due to the potential high risk of infection and haemorrhage if managed expectantly.

Study

First author, year

Appropriate and clearly focused question?¹

Yes/no/unclear

Comprehensive and systematic literature search?²

Yes/no/unclear

Description of included and excluded studies?³

Yes/no/unclear

Description of relevant characteristics of included studies?⁴

Yes/no/unclear

Appropriate adjustment for potential confounders in observational studies?⁵

Yes/no/unclear/notapplicable

Assessment of scientific quality of included studies?⁶

Yes/no/unclear

Enough similarities between studies to make combining them reasonable?⁷

Yes/no/unclear

Potential risk of publication bias taken into account?⁸

Yes/no/unclear

Potential conflicts of interest reported?⁹

Yes/no/unclear

Kim, 2017

Yes

Yes

Yes

Yes

NA

Yes

Yes

Yes

Yes for the systematic review, no for the included studies

Study reference

(first author, publication year)

Describe method of randomisation¹

Bias due to inadequate concealment of allocation?²

(unlikely/likely/unclear)

Bias due to inadequate blinding of participants to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of care providers to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of outcome assessors to treatment allocation?³

(unlikely/likely/unclear)

Bias due to selective outcome reporting on basis of the results?⁴

(unlikely/likely/unclear)

Bias due to loss to follow-up?⁵

(unlikely/likely/unclear)

Bias due to violation of

intention to treat analysis?⁶

(unlikely/likely/unclear)

Lemmers, 2016

‘We randomly assigned women to either expectant management or curettage (1:1), using the web-based application ALEA 2.0 with computer

generated randomization lists.’

Unlikely

Likely,

‘Blinding was not possible due to the nature of the intervention.’

Likely

Unlikely

Unlikely

Unlikely

Unlikely

Al Ma’ani, 2014

‘Randomisation was done by a computer generated list of random numbers.’

Unlikely

Likely

Likely

Unlikely

Unlikely

Unlikely

Unlikely

Nadarajah, 2014

‘Randomisation

was in blocks of ten using a computer-generated random sequence, and sequentially numbered sealed envelopes were prepared and

provided by the study coordinator.’

Unlikely,

the randomisation list was kept by an independent member of staff not involved in the trial.

Likely,

‘no attempt was made to conceal the intervention assignment schedule from the patients or clinicians as the methods for the study groups were obviously different.’

Likely

Unlikely

unlikely

unlikely

Unlikely

Dangalla, 2012

‘Sequentially numbered sealed opaque envelopes with

a card mentioning the study arm were prepared earlier by

the second author. After TVS, uncomplicated patients

(n=160) who fulfilled the criteria (RPC between 15-50 mm

in AP diameter) were randomised to two groups by block

randomisation.’

Unlikely

Likely

Likely

Unlikely

Unlikely

Unclear

Unlikely

Study reference

(first author, year of publication)

Bias due to a non-representative or ill-defined sample of patients?¹

(unlikely/likely/unclear)

Bias due to insufficiently long, or incomplete follow-up, or differences in follow-up between treatment groups?²

(unlikely/likely/unclear)

Bias due to ill-defined or inadequately measured outcome ?³

(unlikely/likely/unclear)

Bias due to inadequate adjustment for all important prognostic factors?⁴

(unlikely/likely/unclear)

Lemmers, 2017

Unlikely

Unlikely

Unlikely

Unlikely

Shokry, 2014

Unlikely

Unlikely

Unlikely

Likely

Tam, 2002

Unlikely

Unlikely

Unlikely

Unlikely