Siristatidis Charalampos S, Sertedaki Eleni, Vaidakis Dennis
Assisted Reproduction Unit, 3rd Department of Obstetrics and Gynaecology, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital,, Rimini 1, Athens, Chaidari, Greece, 12462.
Medical School, National and Kapodistrian University of Athens, 75 M. Assias Street, Goudi, Athens, Greece, 115 27.
Cochrane Database Syst Rev. 2017 May 23;5(5):CD011872. doi: 10.1002/14651858.CD011872.pub2.
In order to overcome the low effectiveness of assisted reproductive technologies (ART) and the high incidence of multiple births, metabolomics is proposed as a non-invasive method to assess oocyte quality, embryo viability, and endometrial receptivity, and facilitate a targeted subfertility treatment.
To evaluate the effectiveness and safety of metabolomic assessment of oocyte quality, embryo viability, and endometrial receptivity for improving live birth or ongoing pregnancy rates in women undergoing ART, compared to conventional methods of assessment.
We searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE, Embase, CINAHL and two trial registers (November 2016). We also examined the reference lists of primary studies and review articles, citation lists of relevant publications, and abstracts of major scientific meetings.
Randomised controlled trials (RCTs) on metabolomic assessment of oocyte quality, embryo viability, and endometrial receptivity in women undergoing ART.
Two review authors independently assessed trial eligibility and risk of bias, and extracted the data. The primary outcomes were rates of live birth or ongoing pregnancy (composite outcome) and miscarriage. Secondary outcomes were clinical pregnancy, multiple and ectopic pregnancy, cycle cancellation, and foetal abnormalities. We combined data to calculate odds ratios (ORs) for dichotomous data and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I² statistic. We assessed the overall quality of the evidence for the main comparisons using GRADE methods.
We included four trials with a total of 802 women, with a mean age of 33 years. All assessed the role of metabolomic investigation of embryo viability. We found no RCTs that addressed the metabolomic assessment of oocyte quality or endometrial receptivity.We found low-quality evidence of little or no difference between metabolomic and non-metabolomic assessment of embryos for rates of live birth or ongoing pregnancy (OR 1.11, 95% CI 0.83 to 1.48; I² = 0%; four RCTs; N = 802), or miscarriage (OR 0.96, 95% CI 0.52 to 1.78; I² = 0%; two RCTs; N = 434). A sensitivity analysis excluding studies at high risk of bias did not change the interpretation of the results for live birth or ongoing pregnancy (OR 0.99, 95% CI 0.71 to 1.38; I² = 0%; two RCTs; N = 621). Our findings suggested that if the rate of live birth or ongoing pregnancy was 36% in the non-metabolomic group, it would be between 32% and 45% with the use of metabolomics.We found low-quality evidence of little or no difference between groups in rates of clinical pregnancy (OR 1.22, 95% CI 0.92 to 1.62; I²= 26%; four trials; N = 802), or multiple pregnancy (OR 1.52, 95% CI 0.71 to 3.23; I² = 0%; two RCTs, N = 181). There was very low-quality evidence of little or no difference between groups in ectopic pregnancy rates (OR 3.37, 95% CI 0.14 to 83.40; one RCT; N = 309), and foetal abnormalities (no events; one RCT; N = 125), and very low-quality evidence of higher rates of cycle cancellation in the metabolomics group (OR 1.78, 95% CI 1.18 to 2.69; I² = 51%; two RCTs; N = 744). Data were lacking on other adverse effects. A sensitivity analysis excluding studies at high risk of bias did not change the interpretation of the results for clinical pregnancy (OR 1.14, 95% CI 0.83 to 1.57; I² = 0%; two RCTs; N = 621).The overall quality of the evidence ranged from very low to low. Limitations included serious risk of bias (associated with poor reporting of methods, attrition bias, selective reporting, and other biases), imprecision, and inconsistency across trials.
AUTHORS' CONCLUSIONS: According to current trials in women undergoing ART, there is insufficient evidence to show that metabolomic assessment of embryos before implantation has any meaningful effect on rates of live birth, ongoing pregnancy, or miscarriage rates. The existing evidence varied from very low to low-quality. Data on adverse events were sparse, so we could not reach conclusions on these. At the moment, there is no evidence to support or refute the use of this technique for subfertile women undergoing ART. Robust evidence is needed from further RCTs, which study the effects on live birth and miscarriage rates for the metabolomic assessment of embryo viability. Well designed and executed trials are also needed to study the effects on oocyte quality and endometrial receptivity, since none are currently available.
为克服辅助生殖技术（ART）有效性低及多胎妊娠发生率高的问题，代谢组学被提出作为一种非侵入性方法，用于评估卵母细胞质量、胚胎活力和子宫内膜容受性，并促进针对性的生育力低下治疗。
与传统评估方法相比，评估代谢组学评估卵母细胞质量、胚胎活力和子宫内膜容受性对提高接受ART治疗的女性活产或持续妊娠率的有效性和安全性。
我们检索了Cochrane妇科与生育组试验注册库、CENTRAL、MEDLINE、Embase、CINAHL以及两个试验注册库（2016年11月）。我们还查阅了主要研究和综述文章的参考文献列表、相关出版物的引用列表以及主要科学会议的摘要。
关于接受ART治疗的女性卵母细胞质量、胚胎活力和子宫内膜容受性的代谢组学评估的随机对照试验（RCT）。
两位综述作者独立评估试验的合格性和偏倚风险，并提取数据。主要结局为活产或持续妊娠率（复合结局）和流产。次要结局为临床妊娠、多胎和异位妊娠、周期取消以及胎儿异常。我们合并数据以计算二分数据的比值比（OR）和95%置信区间（CI）。使用I²统计量评估统计异质性。我们使用GRADE方法评估主要比较的证据总体质量。
我们纳入了4项试验，共802名女性，平均年龄33岁。所有试验均评估了代谢组学研究胚胎活力的作用。我们未发现涉及卵母细胞质量或子宫内膜容受性代谢组学评估的RCT。我们发现低质量证据表明，代谢组学和非代谢组学评估胚胎在活产或持续妊娠率方面几乎没有差异（OR 1.11，95%CI 0.83至1.48；I² = 0%；4项RCT；N = 802），或流产方面（OR 0.96，95%CI 0.52至1.78；I² = 0%；2项RCT；N = 434）。排除高偏倚风险研究的敏感性分析未改变活产或持续妊娠结果的解释（OR 0.99，95%CI 0.71至1.38；I² = 0%；2项RCT；N = 621）。我们的研究结果表明，如果非代谢组学组的活产或持续妊娠率为36%，使用代谢组学时该率将在32%至45%之间。我们发现低质量证据表明，两组在临床妊娠率方面几乎没有差异（OR 1.22，9至1.62；I² = 26%；4项试验；N = 802），或多胎妊娠方面（OR 1.52，95%CI 0.71至3.23；I² = 0%；2项RCT，N = 181）。两组在异位妊娠率方面几乎没有差异的证据质量极低（OR 3.37，95%CI 0.14至83.40；1项RCT；N = 309），以及胎儿异常方面（无事件；1项RCT；N = 125），代谢组学组周期取消率较高的证据质量也极低（OR 1.78，95%CI 1.18至2.69；I² = 51%；2项RCT；N = 744）。缺乏关于其他不良反应的数据。排除高偏倚风险研究的敏感性分析未改变临床妊娠结果的解释（OR 1.14，95%CI 0.83至1.57；I² = 0%；2项RCT；N = 621）。证据的总体质量从极低到低不等。局限性包括严重的偏倚风险（与方法报告不佳、失访偏倚、选择性报告和其他偏倚相关）、不精确性以及各试验之间的不一致性。
根据目前对接受ART治疗女性的试验，没有足够证据表明植入前胚胎的代谢组学评估对活产率、持续妊娠率或流产率有任何有意义的影响。现有证据质量从极低到低不等。关于不良事件的数据稀少，因此我们无法就此得出结论。目前，没有证据支持或反驳对接受ART治疗的生育力低下女性使用该技术。需要进一步的RCT提供有力证据，研究胚胎活力代谢组学评估对活产和流产率的影响。还需要设计良好且执行严格的试验来研究对卵母细胞质量和子宫内膜容受性的影响，因为目前尚无此类试验。
