Supplemental Table 2: Included Case Series

Supplemental Table 2: Included case series

Reference (number) / Study type / Inclusion period / n (+/- FHR) / Primary treatment / Gestational age (weeks) / Success rate / Complications / Severe Complication rate / Fertility (Menstruation pregnancy, birth) / Author's comments and concerns / Conclusion of the present study / Level of evidence (1) / Author Quality Assessment (2) / Country of origin / Published in Journal + impact factor /
Du YJ et al. 2015 (35) / Case series / 2006-2012 / 175 (FHR n/a) / UAE with interarterial MTX (1 mg/kg) + D&C (with bleeding n=35, without bleeding n=140) / 9.3±2.6 / 173/175 / Severe bleeding > 1000 ml (n=5)
Hysterectomy (n=2) / 4% / Normal menses within 4 months. Pregnancies n=11 (Delivery by CS at term n=4, preterm delivery n=3, spontaneous abortion n=4) / Designed as case-control study to investigate potential risk factors for haemorrhage during D&C. Well conducted study. / Increased gestational age increases the risk of bleeding in CSP treated by UAE+MTX+D&C / 4 / H / China / Gynecologic and Obstetric Investigation 1.7
7.3±1.6
Gao et al. 2014 (36) / Case series / 2009-2012 / 119 (+FHR 36) / UAE + D&C (n=93) / 7.1±1.1 / 88/93 / Hysteroscopy (n=3) / 0% / No follow up / Very good presentation of results in a diagramme. But the patients chose their own treatment and there is no follow up. / UAE combined with D&C within 24 hours was an effective and safe uterine preservation treatment for CSP / 4 / M / China / International journal of Gynecology and Obstetrics 1.6
Systemic MTX (50 mg/m2) + D&C (n=26) / 6.9±1.1 / 17/26 / Severe bleeding > 1000 ml (n=3)
Laparotomy (n=7) Perforation of uterus (n=1) / 38.5%
Wang JH et al. 2013 (37) / Case series / 2007-2012 / 91*** (FHR n/a) / UAE + D&C (n=91) / n/a*** / 82/91 / Hysterectomy (n=5) Severe bleeding (n=9) / 9.9% / No follow up / The study was designed to determine risk factors for severe bleeding. Insufficient follow up. / Risk factors for severe bleeding after UAE+ D&C are GA > 8 and gestational mass > 6 cm / 4 / M / China / International journal of Gynecology and Obstetrics 1.6
Wang JH et al. 2009 (38) / Case Series / 2000-2007 / 71 (+FHR 20) / Transabdominal aspiration + local MTX (1 mg/kg) and/or systemic MTX (100 mg) + subsequent D&C by TAS (n=50) / 8.6 ± 3.0 / 45/50 / Severe Bleeding ( n=12) Laparotomy due to bleeding during D&C (n=5) Hysterectomy (n=4) / 24% / No Follow up / The patients chose their own treatment No follow up / Both therapies could treat the majority of CSP patients successfully, but the combined therapy resulted in a shorter time of therapy and indicated a more favorable effect / 4 / M / China / Fertility and Sterility 4.6
Transabdominal aspiration + local MTX (1 mg/kg) and/or systemic MTX (100 mg) (n=21) / 7.5 ± 1.8 / 16/21 / Severe Bleeding (n=7) Laparotomy due to bleeding (n=5) Hysterectomy (n=4) Cesarean scar resection (n=1) / 33%
Wang G et al. 2014 (39) / Case series / 2009-2011 / 71 (FHR n/a) / Laparoscopy (n=32) / 7.7±2.3 / 32/32 / None / 0% / No follow up / The patients chose their own treatment in relation to risk and costs. The converted cases were not thoroughly described in relation to bleeding amount. No follow up / Laparoscopic surgery has the advantage of a high succes rate and low complications. This procedure is especially suitable for exogenous CSP / 4 / H / China / Fertility and Sterility 4.6
Hysteroscopy (n=39) / 7.7±2.3 / 29/39 / Converted to laparoscopy during hysteroscopy (n=2) PostoperativeLaparoscopy (n=2) UAE + MTX (n=3) Postoperative hysteroscopy (n=3) / 0%
Li N et al. 2012 (40) / Case Series / 2008-2010 / 68 (FHR n/a) / Systemic MTX + curettage with hysteroscopy (n=40) (100 mg MTX: n= 15, 150 mg MTX: n=11, 200 mg MTX: n=13) / 6.6 ± 0.7 / 33/40 / Hysterectomy (n=2) UAE due to bleeding - total amount not specified (n=5) / 5% / No Follow up / The patients chose their own treatment - it was the only possible treatment modalities at the hospital Outcomes not properly described / TVS-guided embryo aspiration plus local administration of low-dose MTX is a safe and effective treatment of CSP / 4 / L / China / Ultrasound in Medicine and Biologi 2.1
TVS guided embryo aspiration + local low-dose MTX 100 mg (n=28) / 6.7 ± 0.8 / 28/28 / None / 0%
Yang XY et al. 2010 (41) / Case Series / 2003-2008 / 66
(FHR n/a) / D&C (n=11) / 6.8 (6.0-12.3) / 3/11 / Blood transfusion (n=6) Hysterectomy (n=3) Laparotomy (n=1) / 90.1% / D&C: One induced abortion Syst MTX: One CS at term and one spontanous abortion UAE: One CS at term, two induced abortions / Well-designed study, but the patients chose their own treatment / UAE combined with local MTX is of benefit to women wishing to preserve fertility, and is suitable for use as the primary treatment for CSP / 4 / H / China / BJOG 3.8
Systemic MTX (50 mg/m2)(n=17) / 10/17 / Blood transfusion (n=5) Hysterectomy (n=2) / 41.2%
UAE + local MTX (50 mg) (n=38) / 14/38 / Blood transfusion (n=3) Re-embolization (n=2) Additional D&C (n=24) / 7.9%
Timor-Tritsch et al. 2015 (42) / Case series / 2009-2014 / 60 (+FHR 48) / TVS guided local MTX in the gestational sac and placental site (50 mg) and systemic MTX (25 mg) (n=33) / 6.1-10.4 / 26/33 / UAE (n=2) Foley Catheter (n=5) / 0% / Expected management: Liveborn babies (n=4) (GA 32, 34, 36, 36) and one ongoing pregnancy No additional follow up / CSP diagnose not verified in all, but only suspected. Patients with FHR (n=45) - listed and analysed as 48. Patients with no FHR (n=12). / Combined intramuscular and intragestational MTX injection treatment was successful in treating CSP / 4 / M / USA / Journal of Ultrasound in Medicine 1.5
Systemic MTX (unknown dose) (n=7) (No FHR) / 6.7 (5.1-10.5) / 7/7 / None / 0%
Expectant management (n=4) (No FHR) / 6.5 (5.2-8.0) / 1/4 / Hysterectomy (n=1) UAE (n=2) / 25%
D&C (n=3) / n/a / 2/3 / Hysterectomy (n=1) / 0%
Foley Catheter (n=2) / n/a / 2/2 / None / 0%
UAE (n=1) / n/a / 0/1 / Hysterectomy (n=1) / 0%
Expectant management (n=10) (+ FHR) / 9.6 (6.4-14.0) / 2/10 / Hysterectomy (n=8) / 80%
Cao et al. 2014 (43) / Case Series / 2007-2012 / 54 (+FHR 23) / UAE + D&C + hysteroscopy (n=52) / 7.0 ± 2.1 / 51/52 / Resection of lower uterine segment (n=1) / 0% / Normal menses was reached within 1.6 months (1-3.5). Two pregnancies within the one year follow up (two induced abortions) / Hysteroscopy was not mentioned in the abstract or discussed in the article. / UAE combined with D&C is a safe and efficient treatment for CSP / 4 / H / China / Chin Med Journal 1.0
D&C (n=2) / 0/2 / UAE + D&C due to bleeding (n=2) / 100%
Zhu et al. 2015 (44) / Case series / Jan to Sept 2014 / 53 (+FHR 19) / High-Intensity Focused Ultrasound Ablation with hysteroscopic suction curettage (n=53) / 6.8±0.7 / 49/53 / Uterine perforation (n=1) / 5% / Normal menses within 8 weeks (n=52) / Well-designed study. Interesting and promising novel procedure, but requires special equipment and training / HIFU and hysteroscopic suction curettage is safe and effective when treating patients with CSP at GA less than 8 weeks / 4 / H / China / Medicine 1.0
Liang et al. 2010 (45) / Case Series / 2005-2009 / 52 (FHR n/a) / D&C (n=10) / 5-10.5 / 0/10 / Severe bleeding (n=10) Secondary UAE (n=10) / 100% / Insufficient data / Missing data on patients and outcome. No follow up. / The use of UAE for the treatment of CSP is tolerated well and have few complications. / 4 / L / China / AOGS 2.5
UAE with intra-arteriel MTX (50 mg/m2) followed by D&C (n= 42) / 42/42 / Pain and fever after UAE (n=12) / 0%
Fahg et al. 2009 (46) / Case Series / 2004-2008 / 51 (FHR n/a) / UAE followed by D&C (n=38) / 7.6 ± 1.1 / 38/38 / Haematoma (n=2) Varicose veins 6 months later (n=1) / 0% / No Follow up / Inhomogenous patient groups and insufficient follow up / UAE followed by curettage is recommended to medical facilities where UAE is available / 4 / M / China / Journal of Reproduction and Contraception 0.14
MTX/trichosantin followed by UAE and D&C (n=10) / 7.2 ± 0.6 / 10/10
D&C (n=3) / 8.7 ± 2.1 / 0/3 / Emergency UAE due to bleeding (n=3) / 100%
Cheng LY et al. 2014 (47) / Case series / 2000-2012 / 48 (+ FHR 19) / D&C (n=40) / n/a / 31/40 / Laparoscopy (n=7) UAE (n=1) Laparotomy (n=1) / 2.5% / No follow up / Well described laparoscopic procedure and differentiation between deep and superficial localisation. But insufficient data on "other treatments" and no follow up / D&C is suitable for some types of CSP´s / 4 / M / China / Fertility and Sterility 4.6
Expectant management (n=2) / n/a / 2/2 / None / 0%
Laparotomy (n=2) / n/a / 2/2 / None / 0%
Systemic MTX (50 mg/m2)(n=2) / n/a / 2/2 / None / 0%
Laparoscopy (n=2) / n/a / 2/2 / None / 0%
Wu et al. 2012 (48) / Case Series / 2000-2010 / 47 (+FHR 10) / UAE and intra-arterial MTX infusion (100 mg) (n=22) and subsequent D&C (n=16) / 6.9 ± 1.7 / 22/22 / None / 0% / Normal menses within 1-3 months. One unexpected pregnancy in Syst MTX group - induced abortion / Long inclusion period. The patients chose their own treatment. / UAE combined with intraarterial MTX infusion could be an effective and safe treatment for CSP, however 72% needed subsequent D&C / 4 / M / China / European journal of Obstetrics & Gynecology and Reproductive Biology 1.6
Systemic MTX (50mg/m2) followed by D&C (n=25) / 7.1 ± 1.7 / 23/25 / Severe bleeding (n=2) Laparotomy (n=1) Hysterectomy (n=1) / 12%
Shen et al. 2012 (49) / Case Series / 2008-2010 / 46 (+FHR 8) / UAE with MTX 50 mg followed by D&C after 72 hours (n=25) / 7.9 ± 0.3 / 25/25 / None / 0% / Normal menses within 1 month (n=22), within 3 months (n=3), menstrual disorders (n=16), Dysmenorrhea (n=4). Unwanted pregnancies (n=2) / Well conducted study. Bleeding amount is not specified, which has an implication on the complication rate / UAE and MTX appears to be a safe and effective treatment for CSP and causes less morbidity than current approaches / 4 / H / China / American Journal of Obstetrics and gynecology 4.0
D&C (n=21) / 0/21 / Severe bleeding - amount not specified) (n=12) Subsequent UAE (n=21) Hysterectomy (n=1) / 4.8%
Jiang et al. 2011 (50) / Case Series / 2007-2009 / 45 (FHR n/a) / Systemic MTX (50mg/m2) + D&C. If cardiac activity then local MTX. 7 days after a TAS*guided suction curettage + Foley catheter balloon at the isthmic portion of cervix (n=45) / 7.2 ± 1.6 / 33/45 / Needed further medical treatment for the CSP to disappear (n=12) Hysteroscopy (n=4) Bleeding > 1000 ml. (n=9) UAE (n=3) / 20% / No Follow up / Outcomes described in general terms - specific patient details are missing. No follow up / MTX administration followed by suction curettage followed by Foley tamponade is an effective treatment for CSP / 4 / M / China / European journal of Obstetrics & Gynecology and Reproductive Biology 1.6
Yang Q et al. 2009 (51) / Case Series / 2006-2008 / 39 (FHR n/a) / Hysteroscopy (n=23) / 7.8 (5.4-10.3) / 21/23 / Emergency UAE (n=2) Additional surgery (n=2) / 0% / No Follow up / Inhomogenous patient group due to other first line treatments. Insufficient follow up / Hysteroscopic removal of conceptive tissues implanted in a cesarean section scar seems to be a feasible and safe procedure that might be considered as a treatment option / 4 / M / China / Journal of Minimally Invasive Surgery 1.8
D&C incl vacuum (n=11) / 8.1 (5.4-10.8) / 0/11 / Hysteroscopy (n=11) / 0%
Medical abortion (n=4) / 0/4 / Hysteroscopy (n=4) / 0%
Systemic MTX 50 mg (n=1) / 0/1 / Hysteroscopy and emergency UAE (n=1) / 0%
Le A et al 2013 (52) / Case series / 2008-2012 / 38 (FHR n/a) / UAE with MTX followed by D&C (n=10) / 8.8 ± 2.3 / 10/10 / None / 0% / No pregnancies / No detailed description of the included patients in each group. Only overall averages. Questionable comparability between the groups / Transvaginal surgical approach is efficiant and safe and pregnancy rate was significantly higher in women with endoscopic and vaginal surgery / 4 / M / China / Arch Gynecol Obstet 1.4
Laparoscopy and MTX ( n=2) / 2/2 / None / 0% / Six pregnancies (3 intrauterine, 1 abortion, 2 CSP)
Hysteroscopy and MTX (n=11) / 11/11 / None / 0%
Transvaginal surgery (n=15) / 15/15 / None / 0% / Three intrauterine pregnancies
Michaels et al. 2015 (53) / Case series / 2000-2012 / 34 (+ FHR 22) / Expectant management (n=11) (No FHR n=3) / 6.8±1.6 / 3/11 / Hysterectomy (n=3) / 27.3% / Among the 11 patients with Exp Manag: 5 liveborn babies (29, 32, 36, 36, 39), 3 fetal demise / Retrospectively analysed. Clear description of cases and outcomes, but the groups are not comparable. Only follow up on the women with expectant management / Expectant management offers the possibility of delivering a live-born baby, but carries a substantial likelihood of hysterectomy at delivery. / 4 / H / USA / Journal of Ultrasound in Medicine 2.1
D&C and misoprostol (n=1) / 1/1 / None / 0%
Needle aspiration + KCl injection (n=8) / 6/8 / Hysterectomy (n=1) / 13%
Laparoscopy (n=1) / 1/1 / None / 0%
Ultrasound guided D&C (n=8) / 8/8 / None / 0%
Systemic MTX (unknown dose) (n=3) / 3/3 / None / 0%
Hysterectomy (n=2) / 2/2 / None / 0%
Yin XH et al. 2014 (54) / Case series / 2000-2013 / 34 (FHR n/a) / Needle aspiration with MTX (1 mg/kg)(n=22) / 9.0±5.9 / 19/22 / None / 0% / No follow up / Very poor design. Inconsistencies in presentation of data and no follow up. / Ultrasound guided MTX injection in the gestational sac and UAE with MTX are possible options for treating CSP / 4 / L / China / Journal of Clinical Experimental Medicine 1.3
Systemic MTX (10 mg) (n=8) / 8.0±3.1 / 5/8 / None / 0%