Use of oral progestogen in women with threatened miscarriage in the first trimester: a randomized double-blind controlled trial

Abstract

STUDY QUESTION Will use of oral progestogen in women with threatened miscarriage in the first trimester reduce the miscarriage rate when compared with placebo? SUMMARY ANSWER Use of oral progestogen in women with threatened miscarriage in the first trimester did not reduce miscarriage before 20 weeks when compared with placebo. WHAT IS KNOWN ALREADY Miscarriage is a common complication of pregnancy and occurs in 15–20% of clinically recognized pregnancies. Use of vaginal progestogens is not effective in reducing miscarriage but there is still no good evidence to support use of oral progestogen for the treatment of threatened miscarriage. STUDY DESIGN, SIZE, DURATION This was a randomized double-blind controlled trial. A total of 406 women presenting with threatened miscarriage in the first trimester were recruited from 30 March 2016 to May 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS Women attending Early Pregnancy Assessment Clinics because of vaginal bleeding during the first trimester were recruited and randomly assigned to use dydrogesterone 40 mg orally, followed by 10 mg orally three times a day or placebo until 12 completed weeks of gestation or 1 week after the bleeding stopped, whichever was later. The primary outcome was the miscarriage rate before 20 weeks of gestation. MAIN RESULTS AND THE ROLE OF CHANCE The two groups of women had comparable age, BMI, number of previous miscarriages, gestation and ultrasound findings at presentation. The miscarriage rate before 20 weeks of gestation was similar in both groups, being 12.8% (26/203) in the progestogen group and 14.3% (29/203) in the placebo group (relative risk 0.897, 95% CI 0.548–1.467; P = 0.772). The live birth rate was 81.3% in the progestogen group versus 83.3% in the placebo group (P = 0.697). No significant differences were found between the two groups in terms of obstetric outcomes and side effects. LIMITATIONS, REASONS FOR CAUTION The primary outcome was the miscarriage rate, rather than the live birth rate. Women were recruited from Early Pregnancy Assessment Clinics and those with heavy vaginal bleeding might be admitted into wards directly instead of attending Early Pregnancy Assessment Clinic. The severity of vaginal bleeding was subjectively graded by women themselves. The sample size was not adequate to demonstrate a smaller difference in the miscarriage rate between the progestogen and placebo groups. We did not exclude women with multiple pregnancy, which increased the risk of miscarriage although there was only one set of twin pregnancy in the placebo group. WIDER IMPLICATIONS OF THE FINDINGS Use of oral progestogen is not recommended in women with threatened miscarriage in the first trimester. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the Health and Medical Research Fund, HKSAR (reference number 12132341). All authors declared no conflict of interest. TRIAL REGISTRATION NUMBER ClinicalTrials.gov with an identifier NCT02128685. TRIAL REGISTRATION DATE 1 May 2014. DATE OF FIRST PATIENT'S ENROLMENT 30 March 2016.

A critical appraisal of safety data on dydrogesterone for the support of early pregnancy: a scoping review and meta-analysis

“…Finally, six RCT (Chan et al, 2021;El-Zibdeh, 2005;El-Zibdeh and Yousef, 2009;Griesinger et al, 2018;Pandian, 2009;Tournaye et al, 2017) were selected for meta-analyses (TABLE 1). Notable exclusions (see Supplementary Table for complete list) included a sub-study (Yang et al, 2020) and a single-group trial with no control group (Nadarajah et al, 2017).…”

Pregnancy-related complications and perinatal outcomes following progesterone supplementation before 20 weeks of pregnancy in spontaneously achieved singleton pregnancies: a systematic review and meta-analysis

“…Table S 1 presents the characteristics of the nine eligible trials involving 6439 participants [ 36 – 44 ] and the reasons for exclusion in study selection. Of the 6125 women who were included in the meta-analysis, 3055 women (49.9%) were randomized to the intervention group, and 3070 women (50.1%) were randomized to the control group.…”

Progestogens for preventing miscarriage: a network meta-analysis

“…Four studies were conducted on the threatened miscarriage population (Chan 2020;Coomarasamy 2019;Gerhard 1987;Siew 2018), and three studies in the recurrent miscarriage population MacDonald 1972;Shearman 1963). All studies contributed to the outcome of live birth, with the exception of Shearman 1963 and Siew 2018.…”

“…Four trials (57%) used an adequate method to generate the random sequence and were judged to be at low risk of bias for this domain (Chan 2020;Coomarasamy 2019;Siew 2018).…”