Table 1 Provisional list of trials potentially eligible for inclusion in EPPPIC (progestogen versus placebo/usual care). This table will be updated as new trials are identified. Publication details for individual trials are available on request
EPPPIC identifier | Trial setting | Recruitment years | Progestogen type, dose, intervention, period Comparator | Main indication(s) Gestation at randomization | Singleton/multiple pregnancy | N |
|---|---|---|---|---|---|---|
A: Eligible trials comparing progestogen with standard care or placeboa | ||||||
1 | Single center Egypt (Cairo) | 2008–2009 | Vaginal Micronized progesterone 400 mg suppository daily 18–24 to 37 weeks Placebo | First pregnancy by IVF/ICSI 18–24 weeks | SingletonTwin | 313 |
2 | Single center Iran (Khorramabad) | – | Vaginal Progesterone 100 mg daily 24 to 34 weeks Standard care | Previous SPTBProphylactic cerclage Uterine anomalies Gestation unclear | Singleton | 150 |
3 | Single center Lebanon (Beirut) | 2006–2012 | Intramuscular injection 17-OHPC 250 mg weekly 16–20 to 36 weeks Castor oil | Twin pregnancy 12–20 weeks | Twin | 293 |
4 | Multi center USA | 2004–2006 | Intramuscular injection 17-OHPC 250 mg weekly 16–20 to 35 weeks Castor oil | Triplet pregnancy 16–20 weeks | Triplet | 134 |
5 | Single center Turkey (Istanbul) | 2004–2007 | Vaginal Progesterone 100 mg suppository daily 24 to 34 weeks Placebo | Twin pregnancy Previous SPTB Uterine anomalies 24 weeks | Singleton Twin | 160 |
6 | Multi center USA | 2004–2008 | Intramuscular injection 17-OHPC 250 mg weekly 16–24 to 34 weeks Castor oil | Trichorionic-triamniotic triplet pregnancy 15–23 weeks | Triplet | 81 |
7 | Multi center USA | 2004–2009 | Intramuscular injection 17-OHPC 250 mg weekly 16–24 to 34 weeks Castor oil | Dichorionic-diamniotic twin pregnancy 15–23 weeks | Twin | 240 |
8 | Multi center Australia | 2005–2009 | Vaginal Progesterone 100 mg suppository nightly 20–24 to 34 weeks Placebo | SPTB preceding pregnancy 18–24 weeks | Singleton | 787 |
9 | Single center Brazil (São Paulo) | 1996–2001 | Vaginal Progesterone 100 mg suppository nightly 24 to 34 weeks Placebo | Previous SPTBPrevious cerclage Uterine anomalies Gestation not reported | Singleton | 157 |
10 | Single center Egypt (Cairo) | – | Vaginal Progesterone 200 mg daily 24 to 34 weeks Placebo | Twin pregnancy | Twin | 100 |
11 | Multi center International | 2003–2006 | Vaginal Progesterone 200 mg suppository nightly 24–25 to 34 weeks Safflower oil | Short cervix (≤15 mm) 20–25 weeks | Singleton twin | 250 |
12 | Single center Pilot USA (Ohio) | 2006–2009 | Oral Micronized progesterone 2 × 200 mg capsule daily 16–20 to 34 weeks Placebo | Previous live SPTB < 20 weeks | Singleton | b33 |
13 | Multi center USA | 2007–2011 | Intramuscular injection 17-OHPC 250 mg weekly 16–23 to 37 weeks Castor oil | Nulliparous Short cervix (< 30 mm) 16–23 weeks | Singleton | 657 |
14 | Single center Finland (Oulu) | – | Intramuscular injection 17-OHPC 250 mg weekly 28–33 to 37 weeks Placebo | Twin pregnancy 28–33 weeks | Twin | 77 |
15 | Multi center International | 2008–2010 | Vaginal Progesterone 90 mg gel daily 20–24 to 37 weeks Placebo | Short cervix (10–20 mm) 19–24 weeks | Singleton | 465 |
16 | Single center Egypt (Cairo) | 2006–2008 | Intramuscular injection 17-OHPC 250 mg weekly Second trimester to 36 weeks Saline | Previous SPTB Second trimester | Singleton | 50 |
17 | Single center USA (Baltimore) | – | Intramuscular injection 17-OHPC 250 mg weekly Unclear to 37 weeks Castor oil + benzyl benzoate | 2 previous SPTB 2 SAs or (1 SPTB and 1 SA) in immediately preceding pregnancy < 24 weeks | Singleton Twin | 50 |
18 | Multi center Netherlands | 2006–2009 | Intramuscular injection 17-OHPC 250 mg weekly 16–20 to 36 weeks Castor oil | Multiple pregnancy 15–19 weeks | Twin Triplet Quadruplet | 671 |
19 | Single center India (Chandigarh) | 2004–2006 | Vaginal Micronized progesterone 100 mg capsule nightly 20–24 to 36 weeks Standard care | Previous singleton SPTB 16–24 weeks | Singleton | 100 |
20 | Multi center USA | 1999–2002 | Intramuscular injection 17-OHPC 250 mg weekly 16–20 to 36 weeks Castor oil | Previous SPTB 15–21 weeks | Singleton | 463 |
21 | Single center Albania (Tirana) | – | Intramuscular injection 17-OHPC Dose not reported, daily 15–22 to 34 weeks Oral Progesterone daily (dose not reported, daily 15–22 to 34 weeks Placebo | High risk of SPTB 15–22 weeks | – | 121 |
22 | Multi center UK | 2004–2008 | Vaginal Progesterone 90 mg gel daily 24 to 34 weeks Placebo | Twin pregnancy 22 weeks | Twin | 500 |
23 | Multi center UK | 2009–2013 | Vaginal Progesterone 200 mg suppository nightly 22–24 to 34 weeks Placebo | Previous SPTB Short cervix (≤ 25 mm) Positive FFT and other risk factors for SPTB | Singleton | 1228 |
24 | Multi center USA | 2004–2007 | Vaginal Progesterone 90 mg gel daily 18–23 to 37 weeks Vaginal moisturizer | Singleton SPTB in most recent pregnancy 16–23 weeks | Singleton | 659 |
25 | Single center Iran (Tehran) | Intramuscular injection 17-OHPC 250 mg weekly 16–20 to 34 weeks Placebo | Women ≥ 35 years | – | 260 | |
26 | Single center India (Delhi) | 2005–2006 | Oral Micronized progesterone 100 mg capsule twice daily 18–24 to 36 weeks Placebo | Previous SPTB 18–24 weeks | Singleton | 150 |
27 | Multi center Denmark and Austria | 2006–2008 | Vaginal Micronized progesterone 200 mg suppository daily 20–24 to 34 weeks Safflower oil, gelatine, glycerol, titanium dioxide (E171) | Diamniotic twin pregnancy Chorionicity <16 weeks 18–24 weeks | Multiple | 677 |
28 | Multi center USA | 2004–2006 | Intramuscular injection 17-OHPC 250 mg weekly 16–20 to 35 weeks Castor oil | Twin pregnancy 16–20 weeks | Twin | 661 |
29 | Single center Iran (Mashhad) | 2007–2008 | Intramuscular injection 17-OHPC 250 mg weekly 16 to 37 weeks Standard care | Previous SPTB Not reported | Singleton | 100 |
30 | Multi center France | 2006–2010 | Intramuscular injection 17-OHPC 500 mg twice weekly 24–32 to 36 weeks Standard care | Dichorionic diamniotic twin pregnancy Cervix ≤25 mm 24–32 weeks | Twin | 165 |
31 | Multi center Spain | 2006–2008 | Vaginal Progesterone (1) 2 × 200 mg suppository nightly (2) 1 × 200 mg + 1 × placebo suppository nightly 20 to 34 weeks (3) 2 x placebo suppository nighly Peanut oil + soy lecithin | Dichorionic diamniotic twin pregnancy 20 weeks | Twin | 294 |
32 | Two center Canada (Calgary) | 2006–2010 | Vaginal Progesterone 90 mg gel daily 16–21 to 36 weeks Placebo | Multiple gestation 16–21 weeks | Twin Triplet | 84 |
33 | Single center Brazil (São Paulo) | 2007–2013 | Vaginal Progesterone 200 mg suppository nightly 18–21 to 34 weeks Placebo | Naturally conceived diamniotic twin pregnancy 18–21 weeks | Twin | 390 |
34 | Single center Iran (Tehran) | 2010–2012 | Vaginal Progesterone 400 mg suppository nightly 16–22 to 36 weeks Placebo | Previous SPTB Cervix ≤ 28 mm + cerclage Uterine anomalies Uterine intramural myoma ≥ 7 cm 16–22 weeks | Singleton | 103 |
35 | Two center Egypt (Mansoura) | 2012–2014 | Vaginal Progesterone 400 mg suppository daily 20–24 to 37 weeks Standard care | Dichorionic twin pregnancy Cervix 20–25 mm 20–24 weeks | Twin | 250 |
36 | Multi center Netherlands | 2009–2013 | Vaginal Micronized progesterone 200 mg suppository daily 22 to 34 weeks Placebo | Nulliparous Multiparous without SPTB < 34 weeks gestation Cervix ≤30 mm 18–22 weeks | Singleton | 80 |
37 | Single center India (Shimla) | – | Vaginal Progesterone 100 mg suppository 24–28 to 34 weeks Placebo | Previous SPTB 24–28 weeks | Singleton | 80 |
38 | Single center Pakistan (Bahalwapur) | 2011 | Intramuscular injection 17P 250 mg weekly 16–20 to 36 weeks Placebo | Previous SPTB 16–20 weeks | Singleton | 60 |
45 | Single center USA (Jackson) | – | Intramuscular injection 17-OHCP 250mg weekly Up to 34 weeks or delivery Castor oil | Twin pregnancy 20–30 weeks | Twin | 30 |
B: Eligible trials comparing different types of progestogen | ||||||
21 | Single center Albania (Tirana) | – | Intramuscular injection 17-OHPC Dose not reported, daily 15–22 to 34 weeks Oral Progesterone daily (dose Dose not reported, daily 15–22 to 34 weeks Placebo | High risk of SPTB 15–22 weeks | – | 121 |
39 | Single center Egypt (Tanta) | 2010–2011 | Vaginal Micronized progesterone 200 mg suppository daily 20–24 to 34 weeks Intramuscular injection Progesterone 100 mg every 3rd day 20–24 to 34 weeks | Previous SPTB Cervix ≥ 15 mm 20–24 weeks | Singleton | 160 |
40 | Single center Iran (Yazd) | 2012–2015 | Vaginal Progesterone 200 mg suppository daily 16–20 to delivery Intramuscular injection 17-OHPC 250 mg weekly 16–20 weeks to delivery | Previous SPTB or Cervix < 25 mm (not both) 16–20 weeks | Singleton | 78 |
41 | Single center Saudi Arabia (Khamis Mushayt) | 2009–2011 | Vaginal Micronized progesterone 90 mg gel daily 14–18 to 36 weeks Intramuscular injection 17-OHPC 250 mg weekly 14–18 to 36 weeks | Previous mid-trimester SPTB Previous cerclage 14–18 weeks | Singleton | 518 |
42 | Single center Iran (Tehran) | 2012–2015 | Vaginal Progesterone 400 mg suppository daily 16–24 to 36 weeks 17-OHPC 250 mg weekly 16–24 to 36 weeks | Cervix < 25 mm 16–24 weeks | Singleton | 304 |
43 | Single center USA (Oklahoma) | 2007–2010 | Intramuscular injection 17-OHPC 250 mg weekly 16–21 to 37 weeks Vaginal Micronized progesterone 100 mg suppository daily 16–21 to 37 weeks | Previous live singleton SPTB 16–21 weeks | Singleton | 174 |
44 | Single center Iran (Yazd) | 2010–2011 | Intramuscular injection 17-OHPC 250 mg weekly 16 to 36 weeks Placebo | Assisted conception 16 weeks | Singleton | 106 |