Lim Chi Eung Danforn, Ng Rachel Wai Chung, Cheng Nga Chong Lisa, Zhang George Shengxi, Chen Hui
Faculty of Science, University of Technology Sydney, C/O Specialist Medical Services Group, 356 Homer Street, Earlwood, New South Wales, Australia, 2206.
Cochrane Database Syst Rev. 2019 Jul 2;7(7):CD007689. doi: 10.1002/14651858.CD007689.pub4.
Polycystic ovarian syndrome (PCOS) is characterised by the clinical signs of oligo-amenorrhoea, infertility and hirsutism. Conventional treatment of PCOS includes a range of oral pharmacological agents, lifestyle changes and surgical modalities. Beta-endorphin is present in the follicular fluid of both normal and polycystic ovaries. It was demonstrated that the beta-endorphin levels in ovarian follicular fluid of otherwise healthy women who were undergoing ovulation were much higher than the levels measured in plasma. Given that acupuncture impacts on beta-endorphin production, which may affect gonadotropin-releasing hormone (GnRH) secretion, it is postulated that acupuncture may have a role in ovulation induction via increased beta-endorphin production effecting GnRH secretion. This is an update of our previous review published in 2016.
To assess the effectiveness and safety of acupuncture treatment for oligo/anovulatory women with polycystic ovarian syndrome (PCOS) for both fertility and symptom control.
We identified relevant studies from databases including the Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CNKI, CBM and VIP. We also searched trial registries and reference lists from relevant papers. CENTRAL, MEDLINE, Embase, PsycINFO, CNKI and VIP searches are current to May 2018. CBM database search is to November 2015.
We included randomised controlled trials (RCTs) that studied the efficacy of acupuncture treatment for oligo/anovulatory women with PCOS. We excluded quasi- or pseudo-RCTs.
Two review authors independently selected the studies, extracted data and assessed risk of bias. We calculated risk ratios (RR), mean difference (MD), standardised mean difference (SMD) and 95% confidence intervals (CIs). Primary outcomes were live birth rate, multiple pregnancy rate and ovulation rate, and secondary outcomes were clinical pregnancy rate, restored regular menstruation period, miscarriage rate and adverse events. We assessed the quality of the evidence using GRADE methods.
We included eight RCTs with 1546 women. Five RCTs were included in our previous review and three new RCTs were added in this update of the review. They compared true acupuncture versus sham acupuncture (three RCTs), true acupuncture versus relaxation (one RCT), true acupuncture versus clomiphene (one RCT), low-frequency electroacupuncture versus physical exercise or no intervention (one RCT) and true acupuncture versus Diane-35 (two RCTs). Studies that compared true acupuncture versus Diane-35 did not measure fertility outcomes as they were focused on symptom control.Seven of the studies were at high risk of bias in at least one domain.For true acupuncture versus sham acupuncture, we could not exclude clinically relevant differences in live birth (RR 0.97, 95% CI 0.76 to 1.24; 1 RCT, 926 women; low-quality evidence); multiple pregnancy rate (RR 0.89, 95% CI 0.33 to 2.45; 1 RCT, 926 women; low-quality evidence); ovulation rate (SMD 0.02, 95% CI -0.15 to 0.19, I = 0%; 2 RCTs, 1010 women; low-quality evidence); clinical pregnancy rate (RR 1.03, 95% CI 0.82 to 1.29; I = 0%; 3 RCTs, 1117 women; low-quality evidence) and miscarriage rate (RR 1.10, 95% CI 0.77 to 1.56; 1 RCT, 926 women; low-quality evidence).Number of intermenstrual days may have improved in participants receiving true acupuncture compared to sham acupuncture (MD -312.09 days, 95% CI -344.59 to -279.59; 1 RCT, 141 women; low-quality evidence).True acupuncture probably worsens adverse events compared to sham acupuncture (RR 1.16, 95% CI 1.02 to 1.31; I = 0%; 3 RCTs, 1230 women; moderate-quality evidence).No studies reported data on live birth rate and multiple pregnancy rate for the other comparisons: physical exercise or no intervention, relaxation and clomiphene. Studies including Diane-35 did not measure fertility outcomes.We were uncertain whether acupuncture improved ovulation rate (measured by ultrasound three months post treatment) compared to relaxation (MD 0.35, 95% CI 0.14 to 0.56; 1 RCT, 28 women; very low-quality evidence) or Diane-35 (RR 1.45, 95% CI 0.87 to 2.42; 1 RCT, 58 women; very low-quality evidence).Overall evidence ranged from very low quality to moderate quality. The main limitations were failure to report important clinical outcomes and very serious imprecision.
AUTHORS' CONCLUSIONS: For true acupuncture versus sham acupuncture we cannot exclude clinically relevant differences in live birth rate, multiple pregnancy rate, ovulation rate, clinical pregnancy rate or miscarriage. Number of intermenstrual days may improve in participants receiving true acupuncture compared to sham acupuncture. True acupuncture probably worsens adverse events compared to sham acupuncture.No studies reported data on live birth rate and multiple pregnancy rate for the other comparisons: physical exercise or no intervention, relaxation and clomiphene. Studies including Diane-35 did not measure fertility outcomes as the women in these trials did not seek fertility.We are uncertain whether acupuncture improves ovulation rate (measured by ultrasound three months post treatment) compared to relaxation or Diane-35. The other comparisons did not report on this outcome.Adverse events were recorded in the acupuncture group for the comparisons physical exercise or no intervention, clomiphene and Diane-35. These included dizziness, nausea and subcutaneous haematoma. Evidence was very low quality with very wide CIs and very low event rates.There are only a limited number of RCTs in this area, limiting our ability to determine effectiveness of acupuncture for PCOS.
多囊卵巢综合征（PCOS）的临床特征为月经稀发、不孕和多毛。PCOS的传统治疗方法包括一系列口服药物、生活方式改变和手术方式。β-内啡肽存在于正常卵巢和多囊卵巢的卵泡液中。研究表明，正在排卵的健康女性卵巢卵泡液中的β-内啡肽水平远高于血浆中的水平。鉴于针刺可影响β-内啡肽的产生，而β-内啡肽可能影响促性腺激素释放激素（GnRH）的分泌，因此推测针刺可能通过增加β-内啡肽的产生影响GnRH分泌，从而在诱导排卵中发挥作用。这是我们2016年发表的前一篇综述的更新。
评估针刺治疗多囊卵巢综合征（PCOS）导致的月经稀发/无排卵女性生育能力及症状控制方面的有效性和安全性。
我们从多个数据库中识别相关研究，这些数据库包括妇科与生育组专业注册库、Cochrane系统评价数据库、医学期刊数据库、荷兰医学文摘数据库、心理学文摘数据库、中国知网、中国生物医学文献数据库和中文科技期刊数据库。我们还检索了试验注册库以及相关论文的参考文献列表。Cochrane系统评价数据库、医学期刊数据库、荷兰医学文摘数据库、心理学文摘数据库、中国知网和中文科技期刊数据库的检索截至2018年5月。中国生物医学文献数据库的检索截至2015年11月。
我们纳入了研究针刺治疗PCOS导致的月经稀发/无排卵女性疗效的随机对照试验（RCT）。我们排除了半随机或准随机对照试验。
两位综述作者独立选择研究、提取数据并评估偏倚风险。我们计算了风险比（RR）、平均差（MD）、标准化平均差（SMD）和队列研究的95%置信区间（CI）。主要结局为活产率、多胎妊娠率和排卵率，次要结局为临床妊娠率、月经周期恢复正常、流产率和不良事件。我们使用GRADE方法评估证据质量。
我们纳入了8项RCT，共1546名女性。我们之前的综述纳入了5项RCT，本次更新又增加了3项新的RCT。这些研究比较了真针刺与假针刺（3项RCT）、真针刺与放松疗法（1项RCT）、真针刺与克罗米芬（1项RCT）、低频电针与体育锻炼或不干预（1项RCT）以及真针刺与达英-35（2项RCT）。比较真针刺与达英-35的研究未测量生育结局，因为它们侧重于症状控制。7项研究在至少一个领域存在高偏倚风险。对于真针刺与假针刺，我们无法排除在活产（RR 0.97，95%CI 0.76至1.24；1项RCT，926名女性；低质量证据）、多胎妊娠率（RR 0.89，95%CI 0.33至2.45；1项RCT，926名女性；低质量证据）、排卵率（SMD 0.02，95%CI -0.15至0.19，I = 0%；2项RCT，1010名女性；低质量证据）、临床妊娠率（RR 1.03，95%CI 0.82至1.29；I = 0%；3项RCT，1117名女性；低质量证据）和流产率（RR 1.10，95%CI 0.77至1.56；1项RCT，926名女性；低质量证据）方面存在临床相关差异。与假针刺相比，接受真针刺的参与者的月经周期天数可能有所改善（MD -312.09天，95%CI -344.59至-279.59；1项RCT，141名女性；低质量证据）。与假针刺相比，真针刺可能会使不良事件恶化（RR 1.16，95%CI 1.02至1.31；I = 0%；3项RCT，1230名女性；中等质量证据）。其他比较（体育锻炼或不干预、放松疗法和克罗米芬）未报告活产率和多胎妊娠率的数据。包括达英-35的研究未测量生育结局。我们不确定与放松疗法（MD 0.35，95%CI 0.14至0.56；1项RCT，28名女性；极低质量证据）或达英-35（RR 1.45，95%CI 0.87至2.42；1项RCT，58名女性；极低质量证据）相比，针刺是否能提高排卵率（治疗后三个月通过超声测量）。总体证据质量从极低到中等不等。主要局限性在于未报告重要的临床结局且存在非常严重的不精确性。
对于真针刺与假针刺，我们无法排除在活产率、多胎妊娠率、排卵率、临床妊娠率或流产方面存在临床相关差异。与假针刺相比，接受真针刺的参与者的月经周期天数可能会改善。与假针刺相比，真针刺可能会使不良事件恶化。其他比较（体育锻炼或不干预、放松疗法和克罗米芬）未报告活产率和多胎妊娠率的数据。包括达英-35的研究未测量生育结局，因为这些试验中的女性并非寻求生育。我们不确定与放松疗法或达英-35相比，针刺是否能提高排卵率（治疗后三个月通过超声测量）。其他比较未报告此结局。在针刺组中，体育锻炼或不干预、克罗米芬和达英-35的比较记录了不良事件。这些不良事件包括头晕、恶心和皮下血肿。证据质量极低，置信区间非常宽且事件发生率很低。该领域的随机对照试验数量有限，限制了我们确定针刺治疗PCOS有效性的能力。
