在自体和卵母细胞捐献IVF周期中,向胚胎移植培养基中添加透明质酸(HA)是否可以改善妊娠结局?
现有的最佳证据表明,在自体卵母细胞周期中,向胚胎移植培养基中添加HA在临床上是有益的。
已知将HA添加到胚胎转移培养基中的临床益处,但不知道HA是否不同地影响供体和自体卵母细胞周期。
采用荟萃分析进行系统评价。科克伦妇科和生育小组试验登记册,通过Cochrane在线研究注册中心(CRSO),MEDLINE,搜索Embase和PsycINFO电子数据库(至2020年1月8日),以研究胚胎移植培养基中HA对妊娠结局的影响的随机对照试验(RCT)。
包括具有单独供体和自体卵母细胞数据的RCT,其将具有功能性HA浓度(0.5mg/ml)的胚胎转移培养基与不含或含低HA浓度(0.125mg/ml)的那些进行比较。两名综述作者独立选择纳入试验,提取数据并使用Cochrane偏倚风险评估工具评估纳入的研究。计算集合风险比和95%CI。使用建议分级生成了调查结果汇总表,评估,开发和评估标准。关于证据质量的判断是合理的,并纳入每个结果的报告结果。
15项研究,共有4686名参与者,进行了分析。在自体卵母细胞周期中,当胚胎移植培养基含有功能性HA浓度时,活产从32%增加到39%(风险比(RR)1.22,95%CI1.11-1.34;九项研究,3215名与会者,I2=39%,中等质量证据(治疗所需数量(NNT)14)。富含HA的培养基使临床妊娠和多胎妊娠率分别增加了5%和8%,分别(RR1.11,95%CI1.04-1.18;13项研究,4014名参与者,I2=0%,中等质量的证据,NNT21)和(RR1.49,95%CI1.27-1.76;5项研究,2400名参与者,I2=21%,中等质量的证据,伤害所需的数量13)。相反,在供体卵母细胞周期中,HA添加对活产和临床妊娠影响不大(RR1.1295%CI0.86-1.44;两项研究,317名与会者,I2=50%,低质量证据)和(RR1.06,95%CI0.97-1.28;三项研究,351名参与者,I2=23%,低质量证据)。关于供体卵母细胞周期中多胎妊娠和两组总不良反应的可用信息不足,无法得出结论。
关于供体卵母细胞周期的单独数据和关于卵母细胞质量的有限信息的研究有限。此外,三分之一的纳入研究不包括主要结果,活产率。
有中等水平的证据表明,胚胎移植培养基中的功能性HA浓度会增加临床妊娠,使用自体卵母细胞的IVF周期中的活产和多胎妊娠率。在供体卵母细胞周期中没有看到这种效应,表明供体和自体卵母细胞之间的内在差异或缺乏统计能力。使用自体卵母细胞和单个胚胎移植策略在循环中添加HA到转移培养基中的组合可能会产生最佳组合。具有较高的临床妊娠率和活产率,而不会增加多胎妊娠的机会。
没有获得财政援助。作者没有竞争的利益。
不适用。
Does the addition of hyaluronic acid (HA) to embryo transfer medium improve pregnancy outcomes in both autologous and oocyte donation IVF cycles?
The best available evidence indicates that the addition of HA to embryo transfer medium is clinically beneficial in cycles with autologous oocytes.
There is a known clinical benefit of HA addition to embryo transfer media but it is not known if HA affects donor and autologous oocyte cycles differently.
A systematic
review with meta-analysis was performed. The Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL via Cochrane Register of Studies Online (CRSO), MEDLINE, Embase and PsycINFO electronic databases (until 8 January 2020) were searched for randomized controlled trials (RCTs) examining the effect of HA in embryo transfer medium on pregnancy outcomes.
RCTs with separate donor and autologous oocyte data that compared embryo transfer medium with functional HA concentrations (0.5 mg/ml) to those containing no or low HA concentrations (0.125 mg/ml) were included. Two
review authors independently selected trials for inclusion, extracted data and assessed the included studies using the Cochrane risk of bias assessment tool. Pooled risk ratios and 95% CIs were calculated. A summary of findings table was generated using Grading of Recommendations, Assessment, Development and Evaluation criteria. Judgements about evidence quality were justified and incorporated into the reported results for each outcome.
Fifteen studies, totalling 4686 participants, were analysed. In autologous oocyte cycles, live birth increased from 32% to 39% when embryo transfer media contained functional HA concentrations (risk ratio (RR) 1.22, 95% CI 1.11-1.34; nine studies, 3215 participants, I2 = 39%, moderate-quality evidence (number needed to treat (NNT) 14). HA-enriched media increased clinical pregnancy and multiple pregnancy rates by 5% and 8%, respectively (RR 1.11, 95% CI 1.04-1.18; 13 studies, 4014 participants, I2 = 0%, moderate-quality evidence, NNT 21) and (RR 1.49, 95% CI 1.27-1.76; 5 studies, 2400 participants, I2 = 21%, moderate-quality evidence, number needed to harm 13). Conversely, in donor oocyte cycles, HA addition showed little effect on live birth and clinical pregnancy (RR 1.12 95% CI 0.86-1.44; two studies, 317 participants, I2 = 50%, low-quality evidence) and (RR 1.06, 95% CI 0.97-1.28; three studies, 351 participants, I2 = 23%, low-quality evidence). There was insufficient available information on multiple pregnancy in donor oocyte cycles and on total adverse effects in both groups to draw conclusions.
There were limited studies with separate data on donor oocyte cycles and limited information on oocyte quality. Additionally, one-third of the included studies did not include the main outcome, live birth rate.
There is a moderate level of evidence to suggest that functional HA concentration in embryo transfer medium increases clinical pregnancy, live birth and multiple pregnancy rates in IVF cycles using autologous oocytes. This effect was not seen in donor oocyte cycles, indicating either intrinsic differences between donor and autologous oocytes or lack of statistical power. The combination of HA addition to transfer media in cycles using autologous oocytes and a single embryo transfer policy might yield the best combination, with higher clinical pregnancy and live birth rates without increasing the chance of multiple pregnancies.
No financial assistance was received. The authors have no competing interests.
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