Guideline No. 398: Progesterone for Prevention of Spontaneous Preterm Birth

Objectives To assess the benefits and risks of progesterone therapy for women at increased risk of spontaneous preterm birth (SPB) and to make recommendations for the use of progesterone to reduce the risk of SPB and improve postnatal outcomes. Options To administer or withhold progesterone therapy for women deemed to be at high risk of SPB. Outcomes Preterm birth, neonatal morbidity and mortality, and postnatal outcomes including neurodevelopmental outcomes. Intended Users Maternity care providers, including midwives, family physicians, and obstetricians. Target Population Pregnant women at increased risk of SPB. Evidence Medline, PubMed, EMBASE, and the Cochrane Library were searched from inception to October 2018 for medical subject heading (MeSH) terms and keywords related to pregnancy, preterm birth, previous preterm birth, short cervix, uterine anomalies, cervical conization, neonatal morbidity and mortality, and postnatal outcomes. This document represents an abstraction of the evidence rather than a methodological review. Validation Methods This guideline was reviewed by the Maternal–Fetal Medicine Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) and approved by the SOGC Board of Directors. Benefits, Harms, and/or Costs Therapy with progesterone significantly reduces the risk of SPB in a subpopulation of women at increased risk. Although this therapy entails a cost to the woman in addition to the discomfort associated with its use, no other adverse effects to the mother or the baby have been identified. SUMMARY STATEMENTS (GRADE ratings in parentheses) 1Progesterone therapy reduces the risk of spontaneous preterm birth in women at an increased risk based on history of previous spontaneous preterm birth or in women with a short cervical length (moderate). 2There is insufficient evidence to support the use of progesterone for prevention of spontaneous preterm birth in women with a pregnancy in the absence of cervical shortening (moderate). 3There is insufficient evidence to support the use of progesterone for prevention of spontaneous preterm birth in women with a normal cervical length and a prior conization procedure on the cervix or abnormal uterine anatomy (low). 4Use of progesterone in women with arrested preterm labour is not associated with a reduced risk of spontaneous preterm birth or with improved postnatal outcomes (moderate). 5Use of vaginal progesterone for prevention of spontaneous preterm birth has not been associated with an increase in congenital malformations or with a worsening of postnatal neurodevelopmental outcomes (moderate). RECOMMENDATIONS (GRADE ratings in parentheses) 1In women with a singleton pregnancy and a short cervical length (≤25 mm by transvaginal ultrasound between 16 and 24 weeks), vaginal progesterone therapy for prevention of spontaneous preterm birth is recommended (strong/moderate). 2In women with a previous spontaneous preterm birth, vaginal progesterone therapy for prevention of spontaneous preterm birth is recommended (strong/moderate). 3In women with a twin pregnancy (and by extrapolation of data, with a higher-order multiple pregnancy) and with a short cervical length (≤25 mm by transvaginal ultrasound between 16 and 24 weeks), vaginal progesterone therapy for prevention of spontaneous preterm birth is recommended (strong/moderate). 4In patients with a singleton pregnancy and a previous spontaneous preterm birth or a cervical length ≤25 mm between 16 and 24 weeks in the current pregnancy, if a cerclage is being considered, vaginal progesterone should be offered as an effective and potentially superior alternate therapy (strong/moderate). 5In patients using progesterone for prevention of spontaneous preterm birth, additional therapies such as a cervical cerclage (with exception of a rescue cerclage for an examination-based diagnosis) or a pessary are not recommended (strong/moderate). 6In patients at increased risk of spontaneous preterm birth due to a previous preterm birth, a short cervical length in the current pregnancy, or a multiple pregnancy, bed rest or reduced activity is not recommended (strong/moderate). 7When indicated for prevention of spontaneous preterm birth in a singleton pregnancy, vaginal micronized progesterone in a daily dose of 200 mg is recommended (strong/moderate). 8When indicated for prevention of spontaneous preterm birth in a multiple pregnancy, vaginal micronized progesterone in a daily dose of 400 mg is recommended (conditional [weak]/low). 9When indicated, vaginal progesterone therapy should be initiated between 16 and 24 weeks gestation, depending on when the risked factor is identified (strong/moderate). 10With consideration of individual patient risk factors, vaginal progesterone therapy can be continued up to 34–36 weeks gestation (strong/moderate).