Haas David M, Hathaway Taylor J, Ramsey Patrick S
Indiana University School of Medicine, Department of Obstetrics and Gynecology, 1001 West 10th Street, F-5, Indianapolis, Indiana, USA, 46202.
Uniformed Services University of Health Sciences, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Bethesda, MD, USA.
Cochrane Database Syst Rev. 2019 Nov 20;2019(11):CD003511. doi: 10.1002/14651858.CD003511.pub5.
Progesterone, a female sex hormone, is known to induce secretory changes in the lining of the uterus essential for successful implantation of a fertilized egg. It has been suggested that a causative factor in many cases of miscarriage may be inadequate secretion of progesterone. Therefore, clinicians use progestogens (drugs that interact with the progesterone receptors), beginning in the first trimester of pregnancy, in an attempt to prevent spontaneous miscarriage. This is an update of a review, last published in 2013. Since publication of the 2018 update of this review, we have been advised that the Ismail 2017 study is currently the subject of an investigation by the Journal of Maternal-Fetal & Neonatal Medicine. We have now moved this study from 'included studies' to 'Characteristics of studies awaiting classification' until the outcome of the investigation is known.
To assess the efficacy and safety of progestogens as a preventative therapy against recurrent miscarriage.
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (6 July 2017) and reference lists from relevant articles, attempting to contact trial authors where necessary, and contacted experts in the field for unpublished works.
Randomized or quasi-randomized controlled trials comparing progestogens with placebo or no treatment given in an effort to prevent miscarriage.
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Two reviewers assessed the quality of the evidence using the GRADE approach.
Twelve trials (1,856 women) met the inclusion criteria. Eight of the included trials compared treatment with placebo and the remaining four trials compared progestogen administration with no treatment. The trials were a mix of multicenter and single-center trials, conducted in India, Jordan, UK and USA. In five trials women had had three or more consecutive miscarriages and in seven trials women had suffered two or more consecutive miscarriages. Routes, dosage and duration of progestogen treatment varied across the trials. The majority of trials were at low risk of bias for most domains. Ten trials (1684 women) contributed data to the analyses. The meta-analysis of all women, suggests that there may be a reduction in the number of miscarriages for women given progestogen supplementation compared to placebo/controls (average risk ratio (RR) 0.73, 95% confidence interval (CI) 0.54 to 1.00, 10 trials, 1684 women, moderate-quality evidence). A subgroup analysis comparing placebo-controlled versus non-placebo-controlled trials, trials of women with three or more prior miscarriages compared to women with two or more miscarriages and different routes of administration showed no clear differences between subgroups for miscarriage. None of the trials reported on any secondary maternal outcomes, including severity of morning sickness, thromboembolic events, depression, admission to a special care unit, or subsequent fertility. There was probably a slight benefit for women receiving progestogen seen in the outcome of live birth rate (RR 1.07, 95% CI 1.00 to 1.13, 6 trials, 1411 women, moderate-quality evidence). We are uncertain about the effect on the rate of preterm birth because the evidence is very low-quality (RR 1.13, 95% CI 0.53 to 2.41, 4 trials, 256 women, very low-quality evidence). No clear differences were seen for women receiving progestogen for the other secondary outcomes including neonatal death, fetal genital abnormalities or stillbirth. There may be little or no difference in the rate of low birthweight and trials did not report on the secondary child outcomes of teratogenic effects or admission to a special care unit.
AUTHORS' CONCLUSIONS: For women with unexplained recurrent miscarriages, supplementation with progestogen therapy may reduce the rate of miscarriage in subsequent pregnancies.
孕酮是一种女性性激素，已知其可诱导子宫内膜发生分泌期变化，这对受精卵成功着床至关重要。有人提出，许多流产病例的一个致病因素可能是孕酮分泌不足。因此，临床医生从妊娠早期开始使用孕激素（与孕酮受体相互作用的药物），试图预防自然流产。这是一篇综述的更新版，上次发表于2013年。自本综述2018年更新版发表以来，我们获悉《母婴与新生儿医学杂志》目前正在对伊斯梅尔2017年的研究进行调查。在调查结果出来之前，我们已将这项研究从“纳入研究”移至“待分类研究的特征”。
评估孕激素作为预防复发性流产的治疗方法的疗效和安全性。
对于本次更新，我们检索了Cochrane妊娠与分娩试验注册库、ClinicalTrials.gov、世界卫生组织国际临床试验注册平台（ICTRP）（2017年7月6日）以及相关文章的参考文献列表，必要时试图联系试验作者，并联系该领域的专家获取未发表的研究成果。
比较孕激素与安慰剂或不进行治疗以预防流产的随机或半随机对照试验。
两位综述作者独立评估试验是否纳入以及偏倚风险，提取数据并检查其准确性。两位评审员使用GRADE方法评估证据质量。
12项试验（1856名女性）符合纳入标准。其中8项纳入试验比较了孕激素与安慰剂治疗，其余4项试验比较了孕激素给药与不治疗。这些试验包括多中心和单中心试验，在印度、约旦、英国和美国进行。在5项试验中，女性有3次或更多次连续流产，在7项试验中，女性有2次或更多次连续流产。孕激素治疗的途径、剂量和持续时间在各试验中有所不同。大多数试验在大多数领域的偏倚风险较低。10项试验（1684名女性）为分析提供了数据。对所有女性的荟萃分析表明，与安慰剂/对照组相比，补充孕激素的女性流产数量可能会减少（平均风险比（RR）0.73，95%置信区间（CI）0.54至1.00，10项试验，1684名女性，中等质量证据）。一项亚组分析比较了安慰剂对照试验与非安慰剂对照试验、有3次或更多次既往流产的女性试验与有2次或更多次流产的女性试验以及不同给药途径，结果显示各亚组在流产方面无明显差异。没有一项试验报告任何次要的母亲结局，包括孕吐严重程度、血栓栓塞事件、抑郁症、入住特殊护理病房或后续生育能力。在活产率结局方面，接受孕激素治疗的女性可能略有获益（RR 1.07，95%CI 1.00至1.13，6项试验，1411名女性，中等质量证据）。我们不确定对早产率的影响，因为证据质量非常低（RR 1.13，95%CI 0.53至2.41，4项试验，256名女性，极低质量证据）。接受孕激素治疗的女性在其他次要结局方面没有明显差异，包括新生儿死亡、胎儿生殖器异常或死产。低出生体重率可能几乎没有差异，试验也未报告致畸作用或入住特殊护理病房等次要儿童结局。
对于原因不明的复发性流产女性，补充孕激素治疗可能会降低后续妊娠的流产率。
