BACKGROUND There is a wealth of information regarding interventions for treating subfertility. The majority of studies exploring interventions for improving conception rates also report on pregnancy outcomes. However, there is no efficient way for clinicians, researchers, funding organizations, decision-making bodies or women themselves to easily access and review the evidence for the effect of adjuvant therapies on key pregnancy outcomes in subfertile women. OBJECTIVE AND RATIONALE The aim was to summarize all published systematic reviews (SRs) of randomized controlled trials (RCTs) of interventions in the subfertile population, specifically reporting on the pregnancy outcomes of miscarriage and live birth. Furthermore, we aimed to highlight promising interventions and areas that need high-quality evidence. SEARCH METHODS We searched the Cochrane Database of Systematic Reviews and PubMed clinical queries SR filter (inception until July 2021) with a list of key words to capture all SRs specifying or reporting any miscarriage outcome. Studies were included if they were SRs of RCTs. The population was subfertile women (pregnant or trying to conceive) and any intervention (versus placebo or no treatment) was included. We adopted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) for determining the quality of the evidence. Exclusion criteria were overview reviews, reviews that exclusively reported on women conceiving via natural conception, reviews including non-randomized study designs or reviews where miscarriage or live birth outcomes were not specified or reported. OUTCOMES The primary outcome was miscarriage, defined as pregnancy loss <24 weeks of gestation. Data were also extracted for live birth where available. We included 75 published SRs containing 121 251 participants. There were 14 classes of intervention identified: luteal phase, immunotherapy, anticoagulants, hCG, micronutrients, lifestyle, endocrine, surgical, pre-implantation genetic testing for aneuploidies (PGT-As), laboratory techniques, endometrial injury, ART protocols, other adjuncts/techniques in the ART process and complementary interventions. The interventions with at least moderate-quality evidence of benefit in reducing risk of miscarriage or improving the chance of a live birth are: intrauterine hCG at time of cleavage stage embryo transfer, but not blastocyst transfer, antioxidant therapy in males, dehydroepiandrosterone in women and embryo medium containing high hyaluronic acid. Interventions showing potential increased risk of miscarriage or reduced live birth rate are: embryo culture supernatant injection before embryo transfer in frozen cycles and PGT-A with the use of fluorescence in situ hybridization. WIDER IMPLICATIONS This review provides an overview of key pregnancy outcomes from published SRs of RCTs in subfertile women. It provides access to concisely summarized information and will help clinicians and policy makers identify knowledge gaps in the field, whilst covering a broad range of topics, to help improve pregnancy outcomes for subfertile couples. Further research is required into the following promising interventions: the dose of progesterone for luteal phase support, peripheral blood mononuclear cells for women with recurrent implantation failure, glucocorticoids in women undergoing IVF, low-molecular-weight heparin for unexplained subfertility, intrauterine hCG at the time of cleavage stage embryo or blastocyst transfer and low oxygen concentrations in embryo culture. In addition, there is a need for high-quality, well-designed RCTs in the field of reproductive surgery. Finally, further research is needed to demonstrate the integrated effects of non-pharmacological lifestyle interventions.

中文翻译：

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评估优化生育力低下女性妊娠结局的干预措施和辅助措施：综述

背景技术存在大量关于治疗生育力低下的干预措施的信息。大多数探索提高受孕率干预措施的研究也报告了妊娠结局。然而，临床医生、研究人员、资助组织、决策机构或女性本身没有有效的方法来轻松获取和审查辅助治疗对生育力低下女性关键妊娠结局的影响的证据。目的和理由 目的是总结所有已发表的针对生育力低下人群干预措施的随机对照试验（RCT）的系统评价（SR），特别是报告流产和活产的妊娠结局。此外，我们的目的是强调有希望的干预措施和需要高质量证据的领域。搜索方法 我们使用关键词列表搜索了 Cochrane 系统评价数据库和 PubMed 临床查询 SR 过滤器（截至 2021 年 7 月），以捕获所有指定或报告任何流产结果的 SR。如果研究是 RCT 的 SR，则纳入其中。人群是生育力低下的女性（怀孕或试图怀孕），并且包括任何干预措施（与安慰剂或不治疗相比）。我们采用建议、评估、制定和评价分级（GRADE）来确定证据的质量。排除标准是概述审查、专门报告通过自然受孕的妇女的审查、包括非随机研究设计的审查或未指定或报告流产或活产结果的审查。结果 主要结果是流产，定义为妊娠24周以内的流产。如果有的话，还提取了活产数据。我们纳入了 75 个已发布的 SR，其中包含 121 251 名参与者。确定了 14 类干预措施：黄体期、免疫治疗、抗凝剂、hCG、微量营养素、生活方式、内分泌、手术、植入前非整倍体基因检测 (PGT-As)、实验室技术、子宫内膜损伤、ART 方案、其他辅助措施/ ART 过程中的技术和补充干预措施。在降低流产风险或提高活产机会方面具有至少中等质量证据的干预措施包括：卵裂期胚胎移植时的宫内 hCG，但不是囊胚移植、男性的抗氧化治疗、女性的脱氢表雄酮和含有高透明质酸的胚胎培养基。显示潜在流产风险增加或活产率降低的干预措施包括：冷冻周期胚胎移植前注射胚胎培养物上清液以及使用荧光原位杂交的 PGT-A。更广泛的影响 本综述概述了已发表的不育女性随机对照试验的 SR 中的关键妊娠结局。它提供了对简明总结的信息的访问，并将帮助临床医生和政策制定者确定该领域的知识差距，同时涵盖广泛的主题，以帮助改善生育力低下夫妇的妊娠结局。需要对以下有前途的干预措施进行进一步研究：用于黄体期支持的黄体酮剂量、用于反复着床失败的女性的外周血单核细胞、接受 IVF 的女性的糖皮质激素、用于不明原因生育力低下的低分子量肝素、子宫内 hCG卵裂期胚胎或囊胚移植的时间以及胚胎培养中的低氧浓度。此外，生殖外科领域需要高质量、精心设计的随机对照试验。最后，需要进一步的研究来证明非药物生活方式干预的综合效果。