Table 1 Characteristics of included studies

1.

Blanchard et al. 2005 [14]

Randomized controlled trial

KEM Hospital in Pune, India, and Hungvuong Hospital in Ho Chi Minh City, Vietnam.

Women seeking pregnancy termination at 56 days or less of amenorrhea. All eligible women had a transvaginal ultrasound scan to confirm duration of pregnancy.

Misoprostol oral 400 μg every 3 h for 4 doses (N = 36)

vs.

Misoprostol oral 800 μg every 6 h for 2 doses (N = 24)

vs.

Misoprostol vaginal 600 μg for 1 dose (N = 40)

2.

Blum et al. 2012 [6]

Randomized controlled trial

Two large maternity hospitals: the Centre de Maternite et Neonatologie de la Rabta in Tunisia (n = 193) and Hung Vuong Hospital, Ho Chi Minh City, Vietnam (n = 248).

Pregnant women presenting for early medical abortion up to 63 days since their last menstrual period.

Mifepristone + misoprostol combined

Mifepristone 200 mg on day 1 and 800 μg buccal misoprostol followed by placebo 3 h later on day 2 (N = 220)

vs.

Misoprostol alone

Placebo on day 1 and 1600 μg of misoprostol (2 doses of 800 μg, given 3 h apart) on day 2 (N = 221)

3.

Chai et al. 2013 [18]

Randomized controlled trial

Conducted at the Family Planning Association in Hong Kong.

Healthy women aged 18 years or older who requested termination of pregnancy of up to 63 days’ gestation. A transvaginal ultrasound examination was performed to verify the duration of pregnancy and to determine the gestational age.

Misoprostol buccal

Misoprostol buccal 800 μg (four 200 μg misoprostol buccal and four sublingual placebo) 48 h after receiving mifepristone (N = 45)

vs.

Misoprostol sublingual

Misoprostol sublingual 800 μg (four 200 μg misoprostol sublingual and four buccal placebo) 48 h after receiving mifepristone (N = 45)

4.

Chawdhary et al. 2009 [19]

Randomized controlled trial

Department of Obstetrics and Gynecology, Tribhuvan University Teaching Hospital, Kathmandu, Nepal.

Trans vaginal ultrasound demonstrating an intact single intrauterine pregnancy up to a 63-day period of gestation.

Mifepristone + misoprostol combined

Mifepristone 200 mg on day 1 and vaginal misoprostol 800 μg on day 3 (N = 50)

vs.

Misoprostol alone

Misoprostol vaginal (800 μg) on day 1 and 3 (total dose 1600 μg) (N = 50)

5.

Chong et al. 2012 [9]

Randomized controlled trial

Three clinics in the Republic of Georgia and at Hoc Mon Hospital in Vietnam.

Women who presented for termination of pregnancy with gestations up to 63 days since last menstrual period (LMP).

Misoprostol buccal 400 μg

Misoprostol buccal 400 μg (two 200 μg misoprostol and two placebo pills) 36–48 h after mifepristone (N = 559)

vs.

Misoprostol buccal 800 μg

Misoprostol buccal 800 μg (four 200 μg misoprostol pills) 36–48 h after mifepristone (N = 563)

6.

Coyaji et al. 2007 [20]

Randomized controlled trial

K.E.M. Hospital in Pune (n = 150) and the Health Centre, Larsen and Toubro Limited, Mumbai, India (n = 150).

Women seeking termination of pregnancies could participate if they had amenorrhoea of 8 weeks or less.

Two doses of misoprostol

Two doses of 400 μg oral misoprostol

taken in 3 h interval 48 h after mifepristone (N = 150)

vs.

Single dose of misoprostol

Single dose of 400 μg oral misoprostol and 2 placebo tablets 3 h later 48 h after mifepristone (N = 150)

7.

Creinin et al. 2007 [12]

Randomized controlled trial

Four centers: The University of Pittsburgh, Oregon Health and Science University, Northwestern University, and the University of Southern California. The University of Pittsburgh served as the sponsoring institution.

Healthy women requesting an elective abortion, had an intrauterine pregnancy less than or equal to 63 days of gestation on the day of mifepristone administration as confirmed by vaginal ultrasound.

Misoprostol 800 μg vaginal immediately after taking mifepristone (N = 567)

vs.

Misoprostol 800 μg vaginal misoprostol 24 h after taking mifepristone (N = 561)

8.

Dahiya et al. 2011 [21]

Randomized controlled trial

Postpartum center at PGIMS Rohtak, India.

Healthy women with intrauterine pregnancy < 56 days based on menstrual history and clinical examination.

Misoprostol oral 400 μg 24 h after mifepristone (N = 48)

vs.

Misoprostol sublingual 400 μg 24 h after mifepristone (N = 45)

9.

Dahiya et al. 2012 [7]

Randomized controlled trial

Outpatient department of Obstetrics and Gynecology of Pt BDSharma PGIMS, Rohtak, India.

Women with amenorrhea < 56 days, age > 18 years, request for elective abortion with the indication as per the guidelines of the 1971 MTP act.

Mifepristone + misoprostol combined

Mifepristone 200 mg oral and 800 μg buccal misoprostol after 24 h (N = 50)

vs.

Misoprostol alone

Misoprostol buccal 800 μg (N = 50)

10.

El-Refaey et al. 1994 [22]

Randomized controlled trial

Department of Obstetrics and Gynaecology, University of Aberdeen

Women requesting termination of pregnancy of less than 56 days amenorrhea confirmed by ultrasound scan examination and fulfilling the criteria of the 1967 Abortion Act.

Misoprostol oral 800 μg single dose 36–48 h after mifepristone (N = 75)

vs.

Misoprostol oral 400 μg repeated 2 h later 36–48 h after mifepristone (N = 75)

11.

El-Refaey et al. 1995 [23]

Randomized controlled trial

Fertility-control clinic, Aberdeen Royal Hospitals, Aberdeen, Scotland.

Women requesting termination of pregnancy within 63 days from the onset of amenorrhea and fulfilling the criteria of the 1967 Abortion Act.

Misoprostol oral 800 μg 36–48 h after mifepristone (N = 130)

vs.

Misoprostol vaginal 800 μg 36–48 h after mifepristone (N = 133)

12.

Fekih et al. 2010 [24]

Randomized controlled trial

Department of Obstetrics and Gynecology in Farhat Hached Teaching Hospital, Sousse, Tunisia.

Women requesting 1st trimester abortion of less than or equal to 56 days from their last menstrual period, determined by vaginal probe ultrasound and a maximum embryonic length of 17 mm.

Mifepristone + misoprostol combined

Mifepristone 200 mg followed by 400 μg of oral misoprostol after 48 h (N = 126)

vs.

Misoprostol alone

Misoprostol sublingual 800 μg (repeated every 4 h for up to a maximum of 3 doses) (N = 126)

13.

Goel et al. 2011 [25]

Randomized controlled trial

Obstetrics and Gynaecology Department, MMIMSR, Mullana (Ambala), Haryana, India.

Healthy pregnant women, who were requesting an elective abortion and had a single intrauterine pregnancy of < 7 weeks (49 days) of gestation as confirmed by transvaginal ultrasonography.

Misoprostol vaginal 400 μg simultaneously with mifepristone (N = 40)

vs.

Misoprostol vaginal 400 μg 24 h after mifepristone (N = 40)

14.

Guest et al. 2007 [11]

Randomized controlled trial

Ninewells Hospital, Dundee, Scotland.

An intrauterine pregnancy confirmed on pelvic ultrasound scan, gestation not exceeding 63 days at the administration of mifepristone and participants must be aged 16 years or older, seeking a termination of pregnancy.

Misoprostol vaginal 800 μg after 6 h of mifepristone (N = 225)

vs.

Misoprostol vaginal 800 μg after 36–48 h of mifepristone (N = 225)

15.

Hamoda et al. 2005 [26]

Randomized controlled trial

Aberdeen Royal Infirmary, United Kingdom.

Women with a viable singleton intrauterine pregnancy (confirmed by transvaginal ultrasound scan) requesting medical abortion up to 13 weeks of gestation. Data aggregated by gestational age.

Misoprostol sublingual 600 μg followed 3 h later by a further dose of 400 μg sublingual misoprostol (N = 57)

vs.

Misoprostol vaginal 800 μg followed 3 h later by a further dose of 400 μg vaginal misoprostol (N = 72)

16.

Jain et al. 2002 [27]

Randomized controlled trial

Women’s and Children’s Hospital and affiliated clinics, Los Angeles County-University of Southern California Medical Center and San Francisco General Hospital, University of California, San Francisco, United States.

A total of 250 healthy women desiring termination of pregnancies < 56 days gestation were enrolled.

Mifepristone + misoprostol combined

Mifepristone 200 mg followed after 48 h by 800 μg of vaginal misoprostol (repeated every 24 h for up to a maximum of 3 doses) (N = 125)

vs.

Misoprostol alone

Placebo on day 1 and misoprostol vaginal 800 μg repeated every 24 h for up to a maximum of 3 doses (N = 125)

17.

Middleton et al. 2005 [28]

Randomized controlled trial

Two sites in Rochester, NY, United States.

Women seeking abortion with pregnancies through 56 days LMP.

Misoprostol buccal 800 μg 1–2 days after mifepristone (N = 223)

vs.

Misoprostol vaginal 800 μg 1–2 days after mifepristone (N = 219)

18.

Ngoc et al. 2011 [8]

Randomized controlled trial

Tertiary hospital in Ho Chi Minh City, Vietnam.

Women with gestational age up to 63 days by LMP, living and working within an hour from the hospital desiring medical abortion.

Mifepristone + misoprostol combined

Mifepristone 200 mg followed 24 h later by 800 μg buccal misoprostol followed by placebo 24 h later after misoprostol (N = 202)

vs.

Misoprostol alone

Placebo followed by 800 μg buccal misoprostol repeated 24 and 48 h later (1600 μg total) (N = 198)

19.

Prasad et al. 2009 [29]

Randomized controlled trial

Department of Obstetrics and Gynecology, Maulana Azad Medical College, New Delhi, India.

Women with gestational age up to 49 days confirmed by clinical examination and pelvic ultrasound seeking abortion.

Medical abortion-misoprostol vaginal 800 μg (N = 70)

vs.

Surgical intervention (N = 70)

20.

Raghavan et al. 2009 [30]

Randomized controlled trial

University Clinic, Municipal Clinical Hospital No.1, Chisinau, the Republic of Moldova.

The date of onset of last menses plus pelvic examination were used to calculate gestational age, with ultrasound confirmation as needed.

Misoprostol sublingual 400 μg 24 h after mifepristone (N = 240)

vs.

Misoprostol oral 400 μg 24 h after mifepristone (N = 240)

21.

Raghavan et al. 2010 [31]

Randomized controlled trial

University Clinic, Municipal Clinical Hospital No.1, Chisinau, the Republic of Moldova.

Women with gestational age through 63 days by LMP presenting for abortion. Gestational age was determined by one or more assessment method: last menses method, pelvic examination and ultrasound.

Misoprostol buccal 400 μg 24 h after mifepristone (N = 277)

vs.

Misoprostol sublingual 400 μg 24 h after mifepristone (N = 273)

22.

Schaff et al. 2000 [32]

Randomized controlled trial

Sixteen US primary care and referral abortion facilities.

Participants were at least 18 years old, no more than 56 days pregnant, healthy and desired an abortion.

1) Misoprostol vaginal 800 μg 1 day later after mifepristone (N = 745)

vs.

2) Misoprostol vaginal 800 μg 2 days later after mifepristone (N = 778)

vs.

3) Misoprostol vaginal 800 μg 3 days later after mifepristone (N = 772)

23.

Schaff et al. 2001 [33]

Randomized controlled trial

Multicenter study at 15 sites in United States.

Women no more than 63 days pregnant, confirmed by sonogram, desiring an abortion.

Misoprostol oral 800 μg 24 h after mifepristone and 400 μg, then another 400 μg misoprostol 2 h later, last dose no later than midnight on day 2 (N = 548)

vs.

Misoprostol vaginal 800 μg 24 h after mifepristone (N = 596)

24.

Schaff et al. 2002 [34]

Randomized controlled trial

Multicenter study at 14 sites in United States

Women no more than 63 days pregnant, confirmed by sonogram, desiring an abortion.

1) Misoprostol oral 400 μg 48 h after mifepristone (N = 220)

vs.

2) Misoprostol oral 800 μg 48 h after mifepristone (N = 269)

vs.

3) Misoprostol vaginal 800 μg 48 h after mifepristone (N = 522)

25.

Shannon et al. 2006 [35]

Randomized controlled trial

Three clinics associated with major research universities in Canada; two in major urban areas and one in a periurban area.

Women aged 16 years or older, seeking elective abortion of pregnancies less than 56 days since last menstrual period or on vaginal ultrasound.

1) Misoprostol oral 400 μg 24–48 h after mifepristone (N = 319)

vs.

2) Misoprostol oral 600 μg 24–48 h after mifepristone (N = 319)

vs.

3) Misoprostol vaginal 800 μg 24–48 h after mifepristone (N = 318)

26.

Tang et al. 2003 [36]

Randomized controlled trial

Department of Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China.

Women with gestational age of less than 9 weeks, confirmed by US, requesting legal termination of pregnancy.

Misoprostol sublingual

Misoprostol sublingual 800 μg (and four tablets of vaginal placebo) 48 h after receiving mifepristone (N = 112)

vs.

Misoprostol vaginal

Misoprostol vaginal 800 μg (and four tablets of sublingual placebo) 48 h after receiving mifepristone (N = 112)

27.

Tendler et al. 2015 [37] 

Randomized controlled trial

Department of Obstetrics and Gynecology, Galilee Medical Center, Nahariya, Israel.

Women no more than 55 days gestational age desiring medical abortion.

Misoprostol oral 400 μg 2 h after mifepristone (N = 50)

vs.

Misoprostol oral 400 μg 48 h after mifepristone (N = 50)

28.

Verma et al. 2011 [13]

Randomized controlled trial

Department of Obstetrics and Gynaecology, Hind Institute of Medical Sciences, India.

Women less than 63 days of gestation choosing medical abortion.

Misoprostol vaginal 400 μg 24 h after mifepristone (N = 100)

vs.

Misoprostol vaginal 400 μg 48 h after mifepristone (N = 100)

29.

Verma et al. 2017 [38]

Randomized controlled trial

Department of Obstetrics and Gynaecology, Hind Institute of Medical Sciences, India.

Women up to 63 days of gestation choosing medical abortion.

Misoprostol vaginal 400 μg simultaneously with mifepristone (N = 100)

vs.

Misoprostol vaginal 400 μg 48 h after mifepristone (N = 100)

30.

Von Hertzen et al. 2007 [39]

Randomized controlled trial

Eleven gynecological centers in six countries.

Women with single intra-uterine pregnancy less than or equal to 63 days verified by US, requesting termination of pregnancy.

1) Misoprostol 800 μg sublingual every 3 h × 3 doses (N = 517)

vs.

2) Misoprostol 800 μg sublingual every 12 h × 3 doses (N = 516)

vs.

3) Misoprostol 800 μg vaginal every 3 h × 3 doses (N = 516)

vs.

4) Misoprostol 800 μg vaginal every 12 h × 3 doses (N = 517)

31.

Von Hertzen et al. 2009 [40]

Randomized controlled trial

Thirteen departments of obstetrics and gynecology in nine countries.

Women with 63 days or less gestation verified by ultrasound, requesting termination of pregnancy.

1) Mifepristone 100 mg + misoprostol 800 μg vaginal 24 h later (N = 545)

vs.

2) Mifepristone 100 mg + misoprostol 800 μg vaginal 48 h later (N = 547)

vs.

3) Mifepristone 200 mg + misoprostol 800 μg vaginal 24 h later (N = 544)

vs.

4) Mifepristone 200 mg + misoprostol 800 μg vaginal 48 h later (N = 545)

32.

Von Hertzen et al. 2010 [10]

Randomized controlled trial

Fifteen obstetrics/gynecology departments in ten countries.

Women requesting legal termination of pregnancy at a gestation of up to 63 days.

1) Mifepristone 200 mg + misoprostol 400 μg sublingual 24 h later (N = 751)

vs.

2) Mifepristone 200 mg + misoprostol 800 μg sublingual 24 h later (N = 752)

vs.

3) Mifepristone 200 mg + misoprostol 400 μg vaginal 24 h later (N = 751)

vs.

4) Mifepristone 200 mg + misoprostol 800 μg vaginal 24 h later (N = 751)

33.

Winikoff et al. 2008 [41]

Randomized controlled trial

Seven facilities in the United States.

Women seeking medical abortion with pregnancies not exceeding 63 days since the LMP on the day of the medical abortion. Gestational age was determined by LMP, clinical examination, and/or ultrasonography, as needed.

Misoprostol oral 800 μg 24–36 h after mifepristone (N = 482)

vs.

Misoprostol buccal800 μg 24–36 h after mifepristone (N = 484)