BACKGROUND Recurrent pregnancy loss (RPL) occurs in 1-3% of all couples trying to conceive. No consensus exists regarding when to perform testing for risk factors in couples with RPL. Some guidelines recommend testing if a patient has had two pregnancy losses whereas others advise to test after three losses. OBJECTIVE AND RATIONALE The aim of this systematic review was to evaluate the current evidence on the prevalence of abnormal test results for RPL amongst patients with two versus three or more pregnancy losses. We also aimed to contribute to the debate regarding whether the investigations for RPL should take place after two or three or more pregnancy losses. SEARCH METHODS Relevant studies were identified by a systematic search in OVID Medline and EMBASE from inception to March 2019. A search for RPL was combined with a broad search for terms indicative of number of pregnancy losses, screening/testing for pregnancy loss or the prevalence of known risk factors. Meta-analyses were performed in case of adequate clinical and statistical homogeneity. The quality of the studies was assessed using the Newcastle-Ottawa scale. OUTCOMES From a total of 1985 identified publications, 21 were included in this systematic review and 19 were suitable for meta-analyses. For uterine abnormalities (seven studies, odds ratio (OR) 1.00, 95% CI 0.79-1.27, I2 = 0%) and for antiphospholipid syndrome (three studies, OR 1.04, 95% CI 0.86-1.25, I2 = 0%) we found low quality evidence for a lack of a difference in prevalence of abnormal test results between couples with two versus three or more pregnancy losses. We found insufficient evidence of a difference in prevalence of abnormal test results between couples with two versus three or more pregnancy losses for chromosomal abnormalities (10 studies, OR 0.78, 95% CI 0.55-1.10), inherited thrombophilia (five studies) and thyroid disorders (two studies, OR 0.52, 95% CI: 0.06-4.56). WIDER IMPLICATIONS A difference in prevalence in uterine abnormalities and antiphospholipid syndrome is unlikely in women with two versus three pregnancy losses. We cannot exclude a difference in prevalence of chromosomal abnormalities, inherited thrombophilia and thyroid disorders following testing after two versus three pregnancy losses. The results of this systematic review may support investigations after two pregnancy losses in couples with RPL, but it should be stressed that additional studies of the prognostic value of test results used in the RPL population are urgently needed. An evidenced-based treatment is not currently available in the majority of cases when abnormal test results are present.

中文翻译：

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复发性流产：两次或三次流产后的诊断检查？对文献和荟萃分析的系统综述。

背景技术经常怀孕的流产（RPL）发生在试图怀孕的所有夫妇中，占1-3％。关于何时对RPL夫妇进行风险因素测试尚无共识。一些指南建议测试患者是否有两次妊娠流产，而其他指南则建议在三次流产后进行测验。目的和理由本系统评价的目的是评估在有两次，三次或更多妊娠流产的患者中RPL异常检测结果的普遍性的当前证据。我们还旨在为有关是否应在两胎或三胎或更多怀孕流产后进行RPL的调查的辩论做出贡献。搜索方法自成立至2019年3月，通过在OVID Medline和EMBASE中进行系统搜索来确定相关研究。对RPL的搜索与对表示妊娠流产数，筛查/测试妊娠流产或已知危险因素的普遍性的术语的广泛搜索相结合。在充分的临床和统计同质性的情况下进行荟萃分析。研究质量使用纽卡斯尔-渥太华量表进行评估。结果1985年确定的出版物中，有21篇纳入本系统评价，其中19篇适用于荟萃分析。对于子宫异常（七项研究，比值比（OR）1.00，95％CI 0.79-1.27，I2 = 0％）和抗磷脂综合征（三项研究，OR 1.04，95％CI 0.86-1.25，I2 = 0％），我们发现低质量的证据表明，有两个或三个或三个以上怀孕流产的夫妇之间，异常检测结果的流行率缺乏差异。我们发现没有足够的证据表明因染色体异常（10项研究，或0.78，95％CI 0.55-1.10），遗传性血友病（5项研究）和甲状腺疾病而导致两胎或三胎或更多流产的夫妇之间的异常测试结果发生率存在差异。 （两项研究，或0.52，95％CI：0.06-4.56）。对女性的影响怀孕两次或三次的妇女不太可能在子宫异常和抗磷脂综合征的发生率上有所差异。我们不能排除在两次或三次妊娠流产后进行检测后染色体异常，遗传性血栓形成和甲状腺疾病的患病率差异。这项系统评价的结果可能会支持在RPL夫妇中两次怀孕失败后进行的调查，但应该强调的是，迫切需要对RPL人群中使用的测试结果的预后价值进行进一步的研究。当前，在存在异常测试结果的大多数情况下，目前尚没有基于证据的治疗方法。