Abstract: We included nine randomised clinical trials (involving 861 women). The trials compared Chinese herbal medicines (various formulations) either alone (one trial), or in combination with other pharmaceuticals (seven trials) versus other pharmaceuticals alone. One study compared Chinese herbal medicines and other pharmaceuticals versus psychotherapy. We did not identify any trials comparing Chinese herbal medicines with placebo or no treatment, including bed rest. Various Chinese herbal medicines were used in the different trials (and some of the classical the formulations were modified in the trials). The Western pharmaceutical medicines included tocolytic drugs such as salbutamol and magnesium sulphate; hormonal supplementation with human chorionic gonadotrophin (HCG), progesterone or dydrogesterone; and supportive supplements such as vitamin E, vitamin K and folic acid. Overall, the methodological quality of the included studies was poor with unclear risk of bias for nearly all the 'Risk of bias' domains assessed. Chinese herbal medicines alone versus other pharmaceuticals alone - the live birth rate was no different between the two groups (risk ratio (RR) 1.05; 95% confidence interval (CI) 0.67 to 1.65; one trial, 80 women). No data were available for the outcome of pregnancy rate (continuation of pregnancy after 20 weeks of gestation). In contrast, the continuing pregnancy rate (RR 1.27 95% CI 1.10 to 1.48, two trials, 189 women) and live birth rate (average RR 1.55; 95% CI 1.14 to 2.10; six trials, 601 women, Tau² = 0.10; I² = 73%) were higher among the group of women who received a combination of Chinese herbal medicines and other pharmaceuticals when compared with women who received other pharmaceuticals alone. For Chinese herbal medicines and psychotherapy versus psychotherapy alone (one study) - there was a higher live birth rate (RR 1.32; 95% CI 1.07 to 1.64; one trial, 90 women) in the group of women who received a combination of Chinese herbal medicines and psychotherapy compared to those women who received psychotherapy alone. No data were available on the continuing pregnancy rate for this comparison. Other primary outcomes (maternal adverse effect and toxicity rate and the perinatal adverse effect and toxicity rate) were not reported in most of the included studies. Two trials (341 women) reported that no maternal adverse effects were found (one trial compared (combined) medicines with other pharmaceuticals, and one trial compared combined Chinese herbal medicine alone versus other pharmaceuticals). One trial (Chinese herbal medicine alone versus other pharmaceuticals alone) reported that there were no abnormal fetuses (ultrasound) or after delivery. There were no data reported for any of this review's secondary outcomes. We found limited evidence (from nine studies with small sample sizes and unclear risk of bias) to assess the effectiveness of Chinese herbal medicines for treating unexplained recurrent miscarriage; no data were available to assess the safety of the intervention for the mother or her baby. There were no data relating to any of this review's secondary outcomes. From the limited data we found, a combination of Chinese herbal medicines and other pharmaceuticals (mainly Western medicines) may be more effective than Western medicines alone in terms of the rate of continuing pregnancy and the rate of live births. However, the methodological quality of the included studies was generally poor. A comparison of Chinese herbal medicines alone versus placebo or no treatment (including bed rest) was not possible as no relevant trials were identified. More high-quality studies are needed to further evaluate the effectiveness and safety of Chinese herbal medicines for unexplained recurrent miscarriage. In addition to assessing the effect of Chinese herbal medicines on pregnancy rate and the rate of live births, future studies should also consider safety issues (adverse effects and toxicity for the mother and her baby) as well as the secondary outcomes listed in this review. This review would provide more valuable information if the included studies could overcome the problems in their designs, such as lacking of qualified placebo-controlled trials, applying adequate randomisation methods and avoiding potential bias.

Plain-language summary: Different Chinese herbal medicine formulae (Shou Tai Pill, Yangxi Zaitai Decoction, Bushen Antai Decoction and some modified formulae) were used in the trials. The basic formula mostly contained some common Chinese herbal medicines (Chinese Dodder Seed, Chinese Taxillus Twig, Himalayan Teasel Root, Largehead Atractylodes Rhizome, Donkey-hide Glue, Eucommia Bark, Tangerine Peel, Szechwon Tangshen Root, White Paeony Root, Baical Skullcap Root, Mongolian Milkvetch Root, Chinese Angelica, etc). Western pharmaceutical medicines included tocolytic drugs such as salbutamol and magnesium sulphate, hormonal supplementation with human chorionic gonadotrophin, progesterone or dydrogesterone, and supportive supplements such as vitamin E, vitamin K and folic acid. We searched for evidence on 1 June 2015 and found nine trials (861 women) to assess the effectiveness of the interventions. All trials were methodologically poor and at an unclear risk of bias overall. No trial used placebo, no treatment or bed rest as a control intervention. One trial studied the effectiveness of psychotherapy compared with Chinese herbs. When Chinese herbal medicines were given in combination with other pharmaceuticals they were associated with higher rates of continuous pregnancy beyond 20 weeks (92.1% versus 72.0%, from two trials, involving 189 women) and live births (79.7% versus 44.2% from six trials, involving 601 women) compared to the other pharmaceuticals alone. Live birth rate was not different when comparing Chinese herbal medicines alone and other pharmaceuticals alone (in one trial, involving 80 women). A comparison of continuing pregnancy rate was not available in this trial. Compared with psychotherapy alone, the live birth rate was higher in the group of women who received a combination of Chinese herbal medicine and psychotherapy (91.1% versus 68.9%). The majority of studies did not report any information about adverse effects for the mothers or the babies. Only two trials (involving 341 women) reported that no maternal adverse effects were found (one trial comparing (combined) medicines with other pharmaceuticals and one trial comparing combined Chinese herbal medicine alone versus other pharmaceuticals alone). Only one trial (comparing Chinese herbal medicine alone versus other pharmaceuticals alone) reported that there were no abnormal babies either before or after delivery. No study recorded its limitations in the trial report. It is unclear which Chinese herbal medicines or their combinations are effective. According to the unique diagnosis and classification of Chinese medicine, the preparations (formulae) may differ according to the subtype of recurrent miscarriage. Most Chinese medicine practitioners modify the classical prescriptions depending on the individual clinical presentations. Some herbal medicines were modified from the classical formula for treatment. Therefore, the conclusion on effectiveness in our study could only represent the overall effects of Chinese herbal medicines on recurrent miscarriage in general. In conclusion, combined Chinese herbal medicines and other pharmaceuticals appear more beneficial than other pharmaceuticals alone for unexplained recurrent miscarriage, but the evidence on the effectiveness and safety of Chinese herbal medicines alone as treatment is unclear. We found no data to evaluate the safety and toxicity of this intervention for women and their babies and no data for all of our other maternal and infant outcomes. More high-quality studies are necessary to fully evaluate the utility of Chinese herbal medicines for unexplained recurrent miscarriage.