title: Single versus repeat doses of misoprostol for treatment of early pregnancy loss-a randomized clinical trial.
abstract: Does repeat administration of misoprostol for early pregnancy loss increase the treatment success rate?
  
  
  
  Repeat administration of misoprostol does not increase the treatment success rate, and is associated with more analgesics use.
  
  
  
  Misoprostol reduces the need for surgical evacuation and shortens the time to complete expulsion in patients with early pregnancy loss. However, the impact of repeat doses of misoprostol is not clear.
  
  
  
  A randomized clinical trial was conducted in a single tertiary hospital, recruiting women with early pregnancy loss (<12 weeks), seeking medical treatment, between August 2015 and June 2016. A sample size of 160 patients was sufficient to detect a 30% decrease in treatment success.
  
  
  
  Participants received 800 μg of misoprostol vaginally on Day 1, and were then randomly assigned into two groups: Patients in the single-dose group were evaluated on Day 8. Patients in the repeat-dose group were evaluated on Day 4, when they were given a repeat dose if required, and scheduled for re-evaluation on Day 8. If complete expulsion was not achieved on Day 8 (endometrial thickness >15 mm or the presence of gestational sac on transvaginal sonography), participants underwent surgical evacuation. The primary outcome was treatment success, defined as no need for surgical intervention up to Day 8.
  
  
  
  Final analysis included 87 participants in the single-dose group and 84 participants in the repeat-dose group, out of whom 41 (48.8%) received a second dose. Treatment succeeded in 67 (77%) patients in the single-dose group and 64 (76%) patients in the repeat-dose group (RR 0.98; 95% CI 0.83-1.16; P = 0.89). Patients in the repeat-dose group reported more use of over the counter analgesics (82.1% versus 69.0%, P = 0.04).
  
  
  
  The study was not blinded and our definition of complete expulsion may be debated. Follow-up time was not equal in all participants, since some had a complete expulsion on Day 4 and some underwent emergent D&C before Day 8. This, however, should not affect the primary outcome.
  
  
  
  Our results suggest that a single-dose protocol is superior to a repeat-dose protocol due to a comparable success rate and more favorable outcomes regarding the need for analgesic drugs.
  
  
  
  We did not receive funding for this study and we declare no conflict of interest.
  
  
  
  ClinicalTrials.gov (NCT02515604).
  
  
  
  2 August 2015.
  
  
  
  19 August 2015.
authors.forename: Yossi
authors.initials: Y
authors.lastname: Mizrachi
authors.affiliation: Department of Obstetrics & Gynecology, Edith Wolfson Medical Center, 62 Halochamim St. POB 58100, Holon, Israel, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Israel.
authors.forename: Ann
authors.initials: A
authors.lastname: Dekalo
authors.affiliation: Department of Obstetrics & Gynecology, Edith Wolfson Medical Center, 62 Halochamim St. POB 58100, Holon, Israel, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Israel.
authors.forename: Ohad
authors.initials: O
authors.lastname: Gluck
authors.affiliation: Department of Obstetrics & Gynecology, Edith Wolfson Medical Center, 62 Halochamim St. POB 58100, Holon, Israel, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Miremberg
authors.affiliation: Department of Obstetrics & Gynecology, Edith Wolfson Medical Center, 62 Halochamim St. POB 58100, Holon, Israel, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Israel.
authors.forename: Lotem
authors.initials: L
authors.lastname: Dafna
authors.affiliation: Department of Obstetrics & Gynecology, Edith Wolfson Medical Center, 62 Halochamim St. POB 58100, Holon, Israel, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Israel.
authors.forename: Ohad
authors.initials: O
authors.lastname: Feldstein
authors.affiliation: Department of Obstetrics & Gynecology, Edith Wolfson Medical Center, 62 Halochamim St. POB 58100, Holon, Israel, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Weiner
authors.affiliation: Department of Obstetrics & Gynecology, Edith Wolfson Medical Center, 62 Halochamim St. POB 58100, Holon, Israel, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Israel.
authors.forename: Jacob
authors.initials: J
authors.lastname: Bar
authors.affiliation: Department of Obstetrics & Gynecology, Edith Wolfson Medical Center, 62 Halochamim St. POB 58100, Holon, Israel, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Sagiv
mesh_terms: D015746:Abdominal Pain / Q000188:drug therapy / Q000209:etiology; D000027:Abortion, Incomplete / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology / Q000601:surgery; D000022:Abortion, Spontaneous / Q000503:physiopathology*; D000046:Academic Medical Centers; D000328:Adult; D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use; D003131:Combined Modality Therapy / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D020964:Embryo Loss / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D057194:Intention to Treat Analysis; D007557:Israel; D059012:Lost to Follow-Up; D016595:Misoprostol / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D010120:Oxytocics / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D010352:Patient Dropouts; D011247:Pregnancy; D062606:Tertiary Care Centers; D014463:Ultrasonography; D014619:Vacuum Curettage / Q000009:adverse effects
chemical_list: D000700:Analgesics; D010120:Oxytocics; D016595:Misoprostol
keywords: abortion; cost effectiveness; pregnancy; randomized controlled trial; surgery