PDF(Pubmed)
Abstract：
BACKGROUND: IVF and IUI with ovarian stimulation (IUI-OS) are widely used in managing unexplained infertility. IUI-OS is generally considered first-line therapy, followed by IVF only if IUI-OS is unsuccessful after several attempts. However, there is a growing interest in using IVF for immediate treatment because it is believed to lead to higher live birth rates and shorter time to pregnancy.
OBJECTIVE: Randomized controlled trials (RCTs) comparing IVF versus IUI-OS had varied study designs and findings. Some RCTs used complex algorithms to combine IVF and IUI-OS, while others had unequal follow-up time between arms or compared treatments on a per-cycle basis, which introduced biases. Comparing cumulative live birth rates of IVF and IUI-OS within a consistent time frame is necessary for a fair head-to-head comparison. Previous meta-analyses of RCTs did not consider the time it takes to achieve pregnancy, which is not possible using aggregate data. Individual participant data meta-analysis (IPD-MA) allows standardization of follow-up time in different trials and time-to-event analysis methods. We performed this IPD-MA to investigate if IVF increases cumulative live birth rate considering the time leading to pregnancy and reduces multiple pregnancy rate compared to IUI-OS in couples with unexplained infertility.
METHODS: We searched MEDLINE, EMBASE, CENTRAL, PsycINFO, CINAHL, and the Cochrane Gynaecology and Fertility Group Specialised Register to identify RCTs that completed data collection before June 2021. A search update was carried out in January 2023. RCTs that compared IVF/ICSI to IUI-OS in couples with unexplained infertility were eligible. We invited author groups of eligible studies to join the IPD-MA and share the deidentified IPD of their RCTs. IPD were checked and standardized before synthesis. The quality of evidence was assessed using the Risk of Bias 2 tool.
RESULTS: Of eight potentially eligible RCTs, two were considered awaiting classification. In the other six trials, four shared IPD of 934 women, of which 550 were allocated to IVF and 383 to IUI-OS. Because the interventions were unable to blind, two RCTs had a high risk of bias, one had some concerns, and one had a low risk of bias. Considering the time to pregnancy leading to live birth, the cumulative live birth rate was not significantly higher in IVF compared to that in IUI-OS (4 RCTs, 908 women, 50.3% versus 43.2%, hazard ratio 1.19, 95% CI 0.81-1.74, I2 = 42.4%). For the safety primary outcome, the rate of multiple pregnancy was not significantly lower in IVF than IUI-OS (3 RCTs, 890 women, 3.8% versus 5.2% of all couples randomized, odds ratio 0.78, 95% CI 0.41-1.50, I2 = 0.0%).
CONCLUSIONS: There is no robust evidence that in couples with unexplained infertility IVF achieves pregnancy leading to live birth faster than IUI-OS. IVF and IUI-OS are both viable options in terms of effectiveness and safety for managing unexplained infertility. The associated costs of interventions and the preference of couples need to be weighed in clinical decision-making.
OBJECTIVE: Randomized controlled trials (RCTs) comparing IVF versus IUI-OS had varied study designs and findings. Some RCTs used complex algorithms to combine IVF and IUI-OS, while others had unequal follow-up time between arms or compared treatments on a per-cycle basis, which introduced biases. Comparing cumulative live birth rates of IVF and IUI-OS within a consistent time frame is necessary for a fair head-to-head comparison. Previous meta-analyses of RCTs did not consider the time it takes to achieve pregnancy, which is not possible using aggregate data. Individual participant data meta-analysis (IPD-MA) allows standardization of follow-up time in different trials and time-to-event analysis methods. We performed this IPD-MA to investigate if IVF increases cumulative live birth rate considering the time leading to pregnancy and reduces multiple pregnancy rate compared to IUI-OS in couples with unexplained infertility.
METHODS: We searched MEDLINE, EMBASE, CENTRAL, PsycINFO, CINAHL, and the Cochrane Gynaecology and Fertility Group Specialised Register to identify RCTs that completed data collection before June 2021. A search update was carried out in January 2023. RCTs that compared IVF/ICSI to IUI-OS in couples with unexplained infertility were eligible. We invited author groups of eligible studies to join the IPD-MA and share the deidentified IPD of their RCTs. IPD were checked and standardized before synthesis. The quality of evidence was assessed using the Risk of Bias 2 tool.
RESULTS: Of eight potentially eligible RCTs, two were considered awaiting classification. In the other six trials, four shared IPD of 934 women, of which 550 were allocated to IVF and 383 to IUI-OS. Because the interventions were unable to blind, two RCTs had a high risk of bias, one had some concerns, and one had a low risk of bias. Considering the time to pregnancy leading to live birth, the cumulative live birth rate was not significantly higher in IVF compared to that in IUI-OS (4 RCTs, 908 women, 50.3% versus 43.2%, hazard ratio 1.19, 95% CI 0.81-1.74, I2 = 42.4%). For the safety primary outcome, the rate of multiple pregnancy was not significantly lower in IVF than IUI-OS (3 RCTs, 890 women, 3.8% versus 5.2% of all couples randomized, odds ratio 0.78, 95% CI 0.41-1.50, I2 = 0.0%).
CONCLUSIONS: There is no robust evidence that in couples with unexplained infertility IVF achieves pregnancy leading to live birth faster than IUI-OS. IVF and IUI-OS are both viable options in terms of effectiveness and safety for managing unexplained infertility. The associated costs of interventions and the preference of couples need to be weighed in clinical decision-making.
摘要：
背景：IVF和IUI联合卵巢刺激（IUI-OS）广泛用于治疗无法解释的不孕症。IUI-OS通常被认为是一线治疗，只有当IUI-OS在几次尝试后都不成功时，才进行IVF。然而,人们对使用IVF进行即时治疗越来越感兴趣，因为它被认为会导致更高的活产率和更短的怀孕时间。
目的：比较IVF和IUI-OS的随机对照试验（RCT）有不同的研究设计和发现。一些RCT使用复杂的算法来结合IVF和IUI-OS，而其他人在两组之间的随访时间不相等，或者在每个周期的基础上比较治疗，引入偏见。在一致的时间框架内比较IVF和IUI-OS的累积活产率对于公平的头对头比较是必要的。以前对RCT的荟萃分析没有考虑怀孕所需的时间，这是不可能使用聚合数据。个体参与者数据荟萃分析（IPD-MA）允许在不同试验和时间到事件分析方法中对随访时间进行标准化。我们进行了这种IPD-MA，以调查IVF是否增加了累积活产率，考虑到导致怀孕的时间，并与IUI-OS相比，降低了多胎妊娠率。
方法：我们搜索了MEDLINE，EMBASE,中部,PsycINFO,CINAHL,和Cochrane妇科和生育小组专业登记册，以确定在2021年6月之前完成数据收集的RCT。2023年1月进行了搜索更新。在无法解释的不孕症夫妇中比较IVF/ICSI与IUI-OS的RCT是合格的。我们邀请了符合条件的研究的作者团体加入IPD-MA，并分享他们的RCT的去识别IPD。在合成前检查并标准化IPD。使用偏见风险2工具评估证据质量。
结果：在八个潜在合格的RCT中，两个被认为是等待分类。在其他六项试验中，四名共有934名女性的IPD，其中550个分配给IVF，383个分配给IUI-OS。因为干预措施无法失明，两个RCT有很高的偏倚风险，一个人有一些顾虑,其中一人的偏倚风险很低。考虑到怀孕导致活产的时间，与IUI-OS相比，IVF中的累积活产率并没有显着提高（4个随机对照试验，908个女人,50.3%对43.2%，风险比1.19，95%CI0.81-1.74，I2=42.4%)。对于安全性的主要结果，IVF中的多胎妊娠率并不明显低于IUI-OS（3个RCT，890名女性,3.8%对所有随机分组的夫妇的5.2%，比值比0.78，95%CI0.41-1.50，I2=0.0%）。
结论：没有有力的证据表明，在无法解释的不孕症夫妇中，IVF比IUI-OS更快地实现了妊娠，从而导致了活产。IVF和IUI-OS在治疗无法解释的不孕症的有效性和安全性方面都是可行的选择。在临床决策中需要权衡干预措施的相关成本和夫妇的偏好。
目的：比较IVF和IUI-OS的随机对照试验（RCT）有不同的研究设计和发现。一些RCT使用复杂的算法来结合IVF和IUI-OS，而其他人在两组之间的随访时间不相等，或者在每个周期的基础上比较治疗，引入偏见。在一致的时间框架内比较IVF和IUI-OS的累积活产率对于公平的头对头比较是必要的。以前对RCT的荟萃分析没有考虑怀孕所需的时间，这是不可能使用聚合数据。个体参与者数据荟萃分析（IPD-MA）允许在不同试验和时间到事件分析方法中对随访时间进行标准化。我们进行了这种IPD-MA，以调查IVF是否增加了累积活产率，考虑到导致怀孕的时间，并与IUI-OS相比，降低了多胎妊娠率。
方法：我们搜索了MEDLINE，EMBASE,中部,PsycINFO,CINAHL,和Cochrane妇科和生育小组专业登记册，以确定在2021年6月之前完成数据收集的RCT。2023年1月进行了搜索更新。在无法解释的不孕症夫妇中比较IVF/ICSI与IUI-OS的RCT是合格的。我们邀请了符合条件的研究的作者团体加入IPD-MA，并分享他们的RCT的去识别IPD。在合成前检查并标准化IPD。使用偏见风险2工具评估证据质量。
结果：在八个潜在合格的RCT中，两个被认为是等待分类。在其他六项试验中，四名共有934名女性的IPD，其中550个分配给IVF，383个分配给IUI-OS。因为干预措施无法失明，两个RCT有很高的偏倚风险，一个人有一些顾虑,其中一人的偏倚风险很低。考虑到怀孕导致活产的时间，与IUI-OS相比，IVF中的累积活产率并没有显着提高（4个随机对照试验，908个女人,50.3%对43.2%，风险比1.19，95%CI0.81-1.74，I2=42.4%)。对于安全性的主要结果，IVF中的多胎妊娠率并不明显低于IUI-OS（3个RCT，890名女性,3.8%对所有随机分组的夫妇的5.2%，比值比0.78，95%CI0.41-1.50，I2=0.0%）。
结论：没有有力的证据表明，在无法解释的不孕症夫妇中，IVF比IUI-OS更快地实现了妊娠，从而导致了活产。IVF和IUI-OS在治疗无法解释的不孕症的有效性和安全性方面都是可行的选择。在临床决策中需要权衡干预措施的相关成本和夫妇的偏好。
