Pregnancy · Pregnancy Complications
RRM Academy Synopsis
Early progesterone may lower preeclampsia risk in singleton pregnancy
Progesterone started before 20 weeks may lower preeclampsia risk among women with singleton pregnancies. In a meta-analysis of nine randomized trials, three reported preeclampsia, with an odds ratio of 0.64. Two trials found no evidence of a difference in gestational diabetes risk.
Key Findings
- Preeclampsia: three trials with 2013 treated and 1969 untreated pregnancies gave a pooled odds ratio of 0.64 (95% CI 0.42–0.98), rated moderate-quality evidence.
- In the vaginal progesterone subgroup, the preeclampsia odds ratio was 0.62 (95% CI 0.40–0.96). The other subgroup showed no difference between supplementation and none.
- Gestational diabetes mellitus: two trials gave an odds ratio of 1.02 (95% CI 0.79–1.32), rated low-quality evidence.
- Low birth weight: four trials with 935 participants gave an odds ratio of 0.57 (95% CI 0.34–0.95), moderate-quality evidence that the authors tie to oral dydrogesterone.
- Preterm birth, small for gestational age, placenta previa, placental abruption and perinatal mortality showed no significant differences. The preterm birth odds ratio was 1.02 (95% CI 0.86–1.20).
Interpretation
The paper is a systematic review and meta-analysis. This method combines the results of separate randomized trials into one estimate. The review selected trials of singleton pregnancies conceived without assisted reproduction. Seven trials enrolled women with threatened miscarriage, and two enrolled women with at least three earlier unexplained miscarriages. Seven trials used placebo controls, and eight of the nine eligible trials took place in Asia or Europe. The authors report that the preeclampsia and low birth weight results were affected by a single study. They call for further trials to find the women most likely to benefit.
RRM Context
The ovary makes progesterone after ovulation. The review's introduction links low progesterone with early miscarriage. RRM asks what caused a low level, and a cycle chart records ovulation and the luteal phase.
Abstract
Background
Progesterone supplementation is widely performed in women with threatened miscarriage or a history of recurrent miscarriage; however, the effects of early progesterone supplementation on pregnancy-related complications and perinatal outcomes in later gestational weeks remain unknown.
Methods
Ovid MEDLINE, the Cochrane Library, Embase and ClinicalTrials.gov were searched until April 3rd, 2021. Randomized controlled trials regarding spontaneously achieved singleton pregnancies who were treated with progestogen before 20 weeks of pregnancy and were compared with those women in unexposed control groups were selected for inclusion. We performed pairwise meta-analyses with the random-effects model. The risk of bias was assessed according to the Cochrane Collaboration tool. The primary outcomes included preeclampsia (PE), and gestational diabetes mellitus (GDM), with the results presented as odds ratios (ORs) with 95% confidence intervals (CIs).
Results
We identified nine eligible studies involving 6439 participants. The pooled OR of subsequent PE following early progestogen supplementation was 0.64 (95% CI 0.42-0.98, moderate quality of evidence). A lower OR for PE was observed in the progestogen group when the subgroup analysis was performed in the vaginal subgroup (OR 0.62, 95%CI 0.40-0.96). There was insufficient evidence of a difference in the rate of GDM between pregnant women with early progestogen supplementation and unexposed pregnant women (OR 1.02, 95% CI 0.79-1.32, low quality of evidence). The pooled OR of low birth weight (LBW) following oral dydrogesterone was 0.57 (95% CI 0.34-0.95, moderate quality of evidence). The results were affected by a single study and the total sample size of enrolled women did not reach the required information size.
Conclusion
Use of vaginal micronized progesterone (Utrogestan) in spontaneously achieved singleton pregnancies with threatened miscarriage before 20 weeks of pregnancy may reduce the risk of PE in later gestational weeks. Among spontaneously achieved singleton pregnancies with threatened miscarriage or a history of recurrent miscarriage, use of oral dydrogesterone before 20 weeks of pregnancy may result in a lower risk of LBW in later gestational weeks. However, the available data were not sufficient to reach definitive conclusions, which highlighted the need for future studies.
Topics
Keywords
Low birth weight, Meta-analysis, Preeclampsia, Progesterone, Spontaneous conception
