BACKGROUND Here we describe the consensus guideline methodology, summarise the evidence-based recommendations we provided to the World Health Organisation (WHO) for their consideration in the development of global guidance and present a narrative review on the management of anovulatory infertility in women with polycystic ovary syndrome (PCOS). OBJECTIVE AND RATIONALE The aim of this paper was to present an evidence base for the management of anovulatory PCOS. SEARCH METHODS The evidence to support providing recommendations involved a collaborative process for: (i) identification of priority questions and critical outcomes, (ii) retrieval of up-to-date evidence and exiting guidelines, (iii) assessment and synthesis of the evidence and (iv) the formulation of draft recommendations to be used for reaching consensus with a wide range of global stakeholders. For each draft recommendation, the methodologist evaluated the quality of the supporting evidence that was then graded as very low, low, moderate or high for consideration during consensus. OUTCOMES Evidence was synthesized and we made recommendations across the definition of PCOS including hyperandrogenism, menstrual cycle regulation and ovarian assessment. Metabolic features and the impact of ethnicity were covered. Management includes lifestyle changes, bariatric surgery, pharmacotherapy (including clomiphene citrate (CC), aromatase inhibitors, metformin and gonadotropins), as well as laparoscopic surgery. In-vitro fertilization (IVF) was considered as were the risks of ovulation induction and of pregnancy in PCOS. Approximately 80% of women who suffer from anovulatory infertility have PCOS. Lifestyle intervention is recommended first in women who are obese largely on the basis of general health benefits. Bariatric surgery can be considered where the body mass index (BMI) is ≥35 kg/m2 and lifestyle therapy has failed. Carefully conducted and monitored pharmacological ovulation induction can achieve good cumulative pregnancy rates and multiple pregnancy rates can be minimized with adherence to recommended protocols. CC should be first-line pharmacotherapy for ovulation induction and letrozole can also be used as first-line therapy. Metformin alone has limited benefits in improving live birth rates. Gonadotropins and laparoscopic surgery can be used as second-line treatment. There is no clear evidence for efficacy of acupuncture or herbal mixtures in women with PCOS. For women with PCOS who fail lifestyle and ovulation induction therapy or have additional infertility factors, IVF can be used with the safer gonadotropin releasing hormone (GnRH) antagonist protocol. If a GnRH-agonist protocol is used, metformin as an adjunct may reduce the risk of ovarian hyperstimulation syndrome. Patients should be informed of the potential side effects of ovulation induction agents and of IVF on the foetus, and of the risks of multiple pregnancy. Increased risks for the mother during pregnancy and for the child, including the exacerbating impact of obesity on adverse outcomes, should also be discussed. WIDER IMPLICATIONS This guidance generation and evidence-synthesis analysis has been conducted in a manner to be considered for global applicability for the safe administration of ovulation induction for anovulatory women with PCOS.

中文翻译：

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多囊卵巢综合征女性无排卵性不孕的管理：支持制定全球世卫组织指南的证据分析。


背景在这里，我们描述了共识指南方法，总结了我们向世界卫生组织（WHO）提供的基于证据的建议，供其在制定全球指南时考虑，并对多囊卵巢女性无排卵不孕症的治疗进行了叙述性回顾综合征（多囊卵巢综合症）。目的和基本原理本文的目的是为无排卵 PCOS 的治疗提供证据基础。搜索方法 支持提供建议的证据涉及以下协作过程：(i) 确定优先问题和关键结果，(ii) 检索最新证据和现有指南，(iii) 评估和综合证据以及(iv) 制定建议草案，用于与广泛的全球利益攸关方达成共识。对于每项建议草案，方法学家都会评估支持证据的质量，然后将其分级为极低、低、中等或高，以供达成共识时考虑。结果 综合了证据，我们就 PCOS 的定义提出了建议，包括雄激素过多症、月经周期调节和卵巢评估。涵盖了代谢特征和种族的影响。治疗包括改变生活方式、减肥手术、药物治疗（包括克罗米芬柠檬酸盐 (CC)、芳香酶抑制剂、二甲双胍和促性腺激素）以及腹腔镜手术。多囊卵巢综合症患者考虑体外受精（IVF）以及诱导排卵和妊娠的风险。大约 80% 患有无排卵不孕症的女性患有 PCOS。首先建议肥胖女性进行生活方式干预，主要是基于一般健康益处。 当体重指数（BMI）≥35 kg/m2且生活方式治疗失败时，可以考虑减肥手术。仔细进行和监测药物促排卵可以实现良好的累积妊娠率，并且通过遵守推荐的方案可以将多胎妊娠率降至最低。 CC应该是诱导排卵的一线药物治疗，来曲唑也可以作为一线治疗。单独使用二甲双胍在提高活产率方面的作用有限。促性腺激素和腹腔镜手术可作为二线治疗。没有明确的证据表明针灸或草药混合物对患有多囊卵巢综合症的女性有效。对于生活方式和促排卵治疗失败或有其他不孕因素的 PCOS 女性，可以将 IVF 与更安全的促性腺激素释放激素 (GnRH) 拮抗剂方案结合使用。如果使用 GnRH 激动剂方案，二甲双胍作为辅助药物可能会降低卵巢过度刺激综合征的风险。应告知患者促排卵剂和体外受精对胎儿的潜在副作用以及多胎妊娠的风险。还应该讨论母亲在怀孕期间和孩子面临的风险增加，包括肥胖对不良后果的加剧影响。更广泛的影响 本指南的生成和证据综合分析的方式考虑到对患有 PCOS 的无排卵女性安全进行促排卵的全球适用性。