Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China.
Cochrane Database Syst Rev. 2021 Jun 4;6(6):CD007535. doi: 10.1002/14651858.CD007535.pub4.
Polycystic ovarian syndrome (PCOS) is characterised by both metabolic and reproductive disorders, and affects 5% to 15% of women of reproductive age. Different western medicines have been proposed for PCOS-related subfertility, such as oral contraceptives, insulin sensitisers and laparoscopic ovarian drilling (LOD). Chinese herbal medicines (CHM) have also been used for subfertility caused by PCOS for decades, and are expected to become an alternative treatment for subfertile women with PCOS.
To assess the efficacy and safety of Chinese herbal medicine (CHM) for subfertile women with polycystic ovarian syndrome (PCOS).
We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase and six other databases, from inception to 2 June 2020. In addition, we searched three trials registries, the reference lists of included trials and contacted experts in the field to locate trials.
We included randomised controlled trials (RCTs) comparing CHM versus placebo, no treatment or conventional (western) therapies for the treatment of subfertile women with PCOS.
Two review authors independently screened trials for inclusion, assessed the risk of bias in included studies and extracted data. We contacted primary study authors for additional information. We conducted meta-analyses. We used the odds ratios (ORs) to report dichotomous data, with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods.
We included eight RCTs with 609 participants. The comparisons in the included trials were as follows: CHM versus clomiphene, CHM plus clomiphene versus clomiphene (with or without ethinyloestradiol cyproterone acetate (EE/CPA)), CHM plus follicle aspiration plus ovulation induction versus follicle aspiration plus ovulation induction alone, and CHM plus laparoscopic ovarian drilling (LOD) versus LOD alone. The overall certainty of the evidence for most comparisons was very low. None of the included studies reported the primary outcome, live birth rate. Most studies reported the secondary outcomes, and only one study reported data on adverse events. In trials that compared CHM to clomiphene (with or without LOD in both study arms), we are uncertain of the effect of CHM on pregnancy rates (odds ratio (OR) 1.41, 95% confidence interval (CI) 0.63 to 3.19; I = 28%; 3 studies, 140 participants; very low certainty evidence). Results suggest that if the chance of pregnancy following clomiphene is assumed to be 21.5%, the chance following CHM would vary between 14.7% and 46.7%. No study reported data on adverse events. When CHM plus clomiphene was compared to clomiphene (with or without EE/CPA), there was low certainty evidence of a higher pregnancy rate in the CHM plus clomiphene group (OR 3.06, 95% CI 2.05 to 4.55; I = 10%; 6 studies, 470 participants; low certainty evidence). Results suggest that if the chance of pregnancy following clomiphene is assumed to be 31.5%, the chance following CHM plus clomiphene would vary between 48.5% and 67.7%. No data were reported on adverse events. In trials that compared CHM plus follicle aspiration and ovulation induction to follicle aspiration and ovulation induction alone, we are uncertain of the effect of CHM on pregnancy rates (OR 1.62, 95% CI 0.46 to 5.68; 1 study, 44 women; very low certainty evidence). Results suggest that if the chance of pregnancy following follicle aspiration and ovulation induction is assumed to be 29.2%, the chance following CHM with follicle aspiration and ovulation induction would vary between 15.9% and 70%. Reported adverse events included severe luteinised unruptured follicle syndrome (LUFS) (Peto OR 0.60, 95% CI 0.06 to 6.14; 1 study, 44 women; very low certainty evidence), ovarian hyperstimulation syndrome (OHSS) (Peto OR 0.16, 95% CI 0.00 to 8.19; 1 study, 44 women; very low certainty evidence) or multiple pregnancy (Peto OR 0.60, 95% CI 0.06 to 6.14; 1 study, 44 women; very low certainty evidence). These results suggest that if the chances of LUFS, OHSS, and multiple pregnancy following follicle aspiration and ovulation induction are assumed to be 8.3%, 4.2%, and 8.3% respectively, the chances following CHM with follicle aspiration and ovulation induction would be 0.5% to 35.8%, 0% to 26.3% and 0.5% to 35.8% respectively. In trials that compared CHM plus LOD to LOD alone, we are uncertain if CHM improves pregnancy rates (OR 3.50, 95% CI 0.72 to 17.09; 1 study, 30 women; very low certainty evidence). Results suggest that if the chance of pregnancy following LOD is assumed to be 40%, the chance following CHM with LOD would vary between 32.4% and 91.9%. No data were reported on adverse events. We are uncertain of the results in the comparison groups for all outcomes. The certainty of the evidence for all other comparisons and outcomes was very low. The main limitations in the evidence were failure to report live birth or adverse events, failure to describe study methods in adequate detail and imprecision due to very low event rates and wide CIs.
AUTHORS' CONCLUSIONS: There is insufficient evidence to support the use of CHM for subfertile women with PCOS. No data are available on live birth. We are uncertain of the effect of CHM on pregnancy rates for there is no consistent evidence to indicate that CHM influences fertility outcomes. However, we find that the addition of CHM to clomiphene may improve pregnancy rates, but there is very limited, low certainty evidence for this outcome. Furthermore, there is insufficient evidence on adverse effects to indicate whether CHM is safe. In the future, well-designed, carefully conducted RCTs are needed, with a particular focus on the live birth rate and other safety indexes.
多囊卵巢综合征（PCOS）的特征是代谢和生殖障碍并存，影响着 5%至 15%的育龄妇女。针对 PCOS 相关的生育力低下，已经提出了不同的西药治疗方法，如口服避孕药、胰岛素增敏剂和腹腔镜卵巢钻孔术（LOD）。几十年来，中药（CHM）也一直被用于治疗 PCOS 引起的生育力低下，预计它将成为治疗 PCOS 不孕妇女的另一种治疗方法。
评估中药（CHM）治疗多囊卵巢综合征（PCOS）不孕妇女的疗效和安全性。
我们检索了 Cochrane 妇科和生殖学组专业注册库、CENTRAL、MEDLINE、Embase 和其他六个数据库，检索时间为 2020 年 6 月 2 日。此外，我们还检索了三个试验注册库、纳入试验的参考文献，并联系了该领域的专家以寻找试验。
我们纳入了比较中药与安慰剂、无治疗或常规（西药）治疗多囊卵巢综合征不孕妇女的随机对照试验（RCT）。
两名综述作者独立筛选试验纳入情况，评估纳入研究的偏倚风险并提取数据。我们联系了主要研究作者以获取更多信息。我们进行了荟萃分析。我们使用比值比（OR）报告二分类数据，置信区间（CI）为 95%。我们使用 Grading of Recommendations Assessment, Development and Evaluation（GRADE）方法评估证据的确定性。
我们纳入了八项 RCT，涉及 609 名参与者。纳入试验的比较如下：中药与氯米酚、中药加氯米酚与氯米酚（加或不加炔雌醇环丙孕酮（EE/CPA））、中药加卵泡抽吸加排卵诱导与单纯卵泡抽吸加排卵诱导、中药加腹腔镜卵巢钻孔术（LOD）与单纯 LOD。大多数比较的证据总体确定性为极低。没有一项纳入研究报告主要结局，活产率。大多数研究报告了次要结局，只有一项研究报告了不良事件数据。在比较中药与氯米酚（研究臂中均加或不加 LOD）的试验中，我们对中药对妊娠率的影响结果不确定（OR 1.41，95%CI 0.63 至 3.19；I = 28%；3 项研究，140 名参与者；极低确定性证据）。结果表明，如果假设氯米酚的妊娠率为 21.5%，那么中药的妊娠率可能在 14.7%至 46.7%之间。没有研究报告不良事件数据。当中药加氯米酚与氯米酚（加或不加 EE/CPA）进行比较时，中药加氯米酚组的妊娠率有低确定性证据更高（OR 3.06，95%CI 2.05 至 4.55；I = 10%；6 项研究，470 名参与者；低确定性证据）。结果表明，如果假设氯米酚的妊娠率为 31.5%，那么中药加氯米酚的妊娠率可能在 48.5%至 67.7%之间。没有报告不良事件数据。在比较中药加卵泡抽吸和排卵诱导与单纯卵泡抽吸和排卵诱导的试验中，我们对中药对妊娠率的影响结果不确定（OR 1.62，95%CI 0.46 至 5.68；1 项研究，44 名妇女；极低确定性证据）。结果表明，如果假设卵泡抽吸和排卵诱导后的妊娠率为 29.2%，那么中药加卵泡抽吸和排卵诱导后的妊娠率可能在 15.9%至 70%之间。报告的不良事件包括严重黄素化未破裂卵泡综合征（LUFS）（Peto OR 0.60，95%CI 0.06 至 6.14；1 项研究，44 名妇女；极低确定性证据）、卵巢过度刺激综合征（OHSS）（Peto OR 0.16，95%CI 0.00 至 8.19；1 项研究，44 名妇女；极低确定性证据）或多胎妊娠（Peto OR 0.60，95%CI 0.06 至 6.14；1 项研究，44 名妇女；极低确定性证据）。这些结果表明，如果假设卵泡抽吸和排卵诱导后 LUFS、OHSS 和多胎妊娠的几率分别为 8.3%、4.2%和 8.3%，那么卵泡抽吸和排卵诱导后加用中药的几率可能在 0.5%至 35.8%、0%至 26.3%和 0.5%至 35.8%之间。在比较中药加 LOD 与单纯 LOD 的试验中，我们对中药是否能提高妊娠率结果不确定（OR 3.50，95%CI 0.72 至 17.09；1 项研究，30 名妇女；极低确定性证据）。结果表明，如果假设 LOD 后的妊娠率为 40%，那么中药加 LOD 的妊娠率可能在 32.4%至 91.9%之间。没有报告不良事件数据。我们对所有结局的对照组结果均不确定。所有其他比较和结局的证据确定性都非常低。证据中的主要限制因素是没有报告活产或不良事件，没有充分描述研究方法，以及由于事件发生率低且置信区间宽导致的不精确性。
目前尚无足够证据支持中药用于治疗多囊卵巢综合征不孕妇女。没有关于活产的数据。我们对中药对妊娠率的影响结果不确定，因为没有一致的证据表明中药会影响生育结局。然而，我们发现，在氯米酚中加入中药可能会提高妊娠率，但这一结果的低确定性证据非常有限。此外，关于不良影响的证据不足，无法确定中药是否安全。未来，需要精心设计和进行的高质量 RCT，特别关注活产率和其他安全性指标。
