School of Reproductive and Developmental Medicine, University of Liverpool, Liverpool Women's Hospital, Crown Street, Liverpool, L8 7SS, UK.
Trials. 2009 Nov 10;10:102. doi: 10.1186/1745-6215-10-102.
Idiopathic recurrent miscarriage is defined as 3 consecutive pregnancy losses with no contributing features found on investigations. At present there are no treatments of proven efficacy for idiopathic recurrent miscarriage. Uterine natural killer (uNK) cells, the most predominant leucocyte in the endometrium are adjacent to foetal trophoblast cells and thought to be involved in implantation. The exact mechanisms of how uNK cells affect implantation are not clear but are probably through the regulation of angiogenesis. Multiple studies have shown an association between high density of uterine natural killer cells and recurrent miscarriage. We have shown that prednisolone reduces the number of uNK cells in the endometrium. The question remains as to whether reducing the number of uNK cells improves pregnancy outcome.
We propose a randomised, double-blind, placebo controlled trial of prednisolone with a pilot phase to assess feasibility of recruitment, integrity of trial procedures, and to generate data to base future power calculations. The primary aim is to investigate whether prednisolone therapy during the first trimester of pregnancy is able to improve live birth rates in patients with idiopathic recurrent miscarriage and raised uNK cells in the endometrium. Secondary outcomes include conception rate, karyotype of miscarriage, miscarriages (first and second trimester), stillbirths, pregnancy complications, gestational age at delivery, congenital abnormality and side effects of steroids. The trial has 2 stages: i) screening of non-pregnant women and ii) randomisation of the pregnant cohort. All patients who fit the inclusion criteria (<40 years old, > or =3 consecutive miscarriages with no cause found and no contraindications to prednisolone therapy) will be asked to consent to an endometrial biopsy in the mid-luteal phase to assess their levels of uNK cells. Women with high levels of uNK cells (> or =5%), will be randomised to either prednisolone or placebo when a pregnancy is confirmed. Follow-up includes 2 weekly ultrasound scans in the first trimester, an anomaly scan at 20 weeks gestation, growth scans at 28 and 34 weeks gestation and a postnatal follow-up at 6 weeks.
Current Controlled Trials ISRCTN28090716.
特发性复发性流产定义为连续 3 次妊娠丢失，且无调查发现的致病特征。目前，特发性复发性流产尚无经证实有效的治疗方法。子宫自然杀伤（uNK）细胞是子宫内膜中最主要的白细胞，与胎儿滋养层细胞相邻，被认为参与着床。uNK 细胞如何影响着床的确切机制尚不清楚，但可能通过调节血管生成。多项研究表明，uNK 细胞密度高与复发性流产有关。我们已经表明，泼尼松龙可减少子宫内膜中的 uNK 细胞数量。但问题是，减少 uNK 细胞数量是否能改善妊娠结局。
我们提出了一项随机、双盲、安慰剂对照的泼尼松龙试验，同时进行了一项试验前期研究，以评估招募的可行性、试验程序的完整性，并生成数据以支持未来的效能计算。主要目的是研究在特发性复发性流产和子宫内膜 uNK 细胞升高的患者中，妊娠早期使用泼尼松龙治疗是否能够提高活产率。次要结局包括受孕率、流产（第一和第二孕期）、死胎、妊娠并发症、分娩时的胎龄、先天性异常和类固醇的副作用。该试验有 2 个阶段：i）对非孕妇进行筛查，ii）对妊娠队列进行随机分组。所有符合纳入标准的患者（<40 岁，连续 3 次流产，无病因发现，无泼尼松龙治疗禁忌）都将被要求同意在黄体中期进行子宫内膜活检，以评估其 uNK 细胞水平。如果发现 uNK 细胞水平较高（>或=5%）的妇女怀孕，将在确认怀孕后随机分为泼尼松龙组或安慰剂组。随访包括妊娠早期每 2 周进行 1 次超声检查、妊娠 20 周时进行 1 次畸形扫描、妊娠 28 周和 34 周时进行生长扫描以及产后 6 周时进行随访。
当前对照试验 ISRCTN28090716。
