PDF(Pubmed)
Abstract：
BACKGROUND: Male factor infertility affect up to 50% of couples unable to conceive spontaneously. Several non-hormonal pharmacological treatments have been proposed to boost spermatogenesis and increase chances of conception in men with infertility. Still, no clear evidence exists on the most effective treatment strategy.
OBJECTIVE: We aimed to compare the effectiveness of non-hormonal pharmacological treatment options for men with infertility using a systematic review and network meta-analysis.
METHODS: We searched MEDLINE, EMBASE, and CENTRAL until October 2023 for randomised/quasi-randomised trials that evaluated any non-hormonal pharmacological treatment options for men with idiopathic semen abnormalities or those with hypogonadism. We performed pairwise and network meta-analyses using a random effect model. We assessed risk of bias, heterogeneity, and network inconsistency. We calculated the mean rank and the surface under the cumulative ranking curve (SUCRA) for each intervention the maximum likelihood to achieve each of reported outcomes. We reported primarily on sperm concentration and other important semen and biochemical outcomes using standardised mean difference (SMD) and 95% confidence-intervals(CI).
RESULTS: We included 14 randomised trials evaluating four treatments (Clomiphene citrate, Tamoxifen, Aromatase inhibitors, anti-oxidants) and their combinations in 1342 men. The overall quality of included trials was low. Sperm concentration improved with clomiphene compared to anti-oxidants (SMD 2.15, 95%CI 0.78-3.52), aromatase inhibitor (SMD 2.93, 95%CI 1.23-4.62), tamoxifen (SMD - 1.96, 95%CI -3.57; -0.36) but not compared to placebo (SMD - 1.53, 95%CI -3.52- 0.47). Clomiphene had the highest likelihood to achieve the maximum change in sperm concentration (SUCRA 97.4). All treatments showed similar effect for sperm motility, semen volume, and normal sperm morphology. FSH levels showed significant improvement with clomiphene vs.anti-oxidant (SMD 1.48, 95%CI 0.44-2.51) but not compared to placebo. The evidence networks for LH and testosterone suffered from significant inconsistency (p = 0.01) with similar trend of improvement with clomiphene compared to other treatments but not compared to placebo.
CONCLUSIONS: There is insufficient evidence to support the routine use of Clomiphene, tamoxifen, and aromatase inhibitors to optimise semen parameters in men with infertility. Future randomised trials are needed to confirm the efficacy of clomiphene in improving fertility outcomes in men.
UNASSIGNED: CRD42023430179.
OBJECTIVE: We aimed to compare the effectiveness of non-hormonal pharmacological treatment options for men with infertility using a systematic review and network meta-analysis.
METHODS: We searched MEDLINE, EMBASE, and CENTRAL until October 2023 for randomised/quasi-randomised trials that evaluated any non-hormonal pharmacological treatment options for men with idiopathic semen abnormalities or those with hypogonadism. We performed pairwise and network meta-analyses using a random effect model. We assessed risk of bias, heterogeneity, and network inconsistency. We calculated the mean rank and the surface under the cumulative ranking curve (SUCRA) for each intervention the maximum likelihood to achieve each of reported outcomes. We reported primarily on sperm concentration and other important semen and biochemical outcomes using standardised mean difference (SMD) and 95% confidence-intervals(CI).
RESULTS: We included 14 randomised trials evaluating four treatments (Clomiphene citrate, Tamoxifen, Aromatase inhibitors, anti-oxidants) and their combinations in 1342 men. The overall quality of included trials was low. Sperm concentration improved with clomiphene compared to anti-oxidants (SMD 2.15, 95%CI 0.78-3.52), aromatase inhibitor (SMD 2.93, 95%CI 1.23-4.62), tamoxifen (SMD - 1.96, 95%CI -3.57; -0.36) but not compared to placebo (SMD - 1.53, 95%CI -3.52- 0.47). Clomiphene had the highest likelihood to achieve the maximum change in sperm concentration (SUCRA 97.4). All treatments showed similar effect for sperm motility, semen volume, and normal sperm morphology. FSH levels showed significant improvement with clomiphene vs.anti-oxidant (SMD 1.48, 95%CI 0.44-2.51) but not compared to placebo. The evidence networks for LH and testosterone suffered from significant inconsistency (p = 0.01) with similar trend of improvement with clomiphene compared to other treatments but not compared to placebo.
CONCLUSIONS: There is insufficient evidence to support the routine use of Clomiphene, tamoxifen, and aromatase inhibitors to optimise semen parameters in men with infertility. Future randomised trials are needed to confirm the efficacy of clomiphene in improving fertility outcomes in men.
UNASSIGNED: CRD42023430179.
摘要：
背景：男性因素不育症影响高达50％的无法自发受孕的夫妇。已经提出了几种非激素药物治疗方法来促进精子发生并增加不育男性的受孕机会。尽管如此，没有明确的证据表明最有效的治疗策略.
目的：我们旨在使用系统评价和网络荟萃分析比较非激素药物治疗方案对男性不孕症的有效性。
方法：我们搜索了MEDLINE，EMBASE,和CENTRAL，直到2023年10月进行随机/半随机试验，评估特发性精液异常或性腺功能减退男性的任何非激素药物治疗方案。我们使用随机效应模型进行了成对和网络荟萃分析。我们评估了偏见的风险，异质性，网络不一致。我们计算了每个干预措施实现每个报告结果的最大可能性的平均排名和累积排名曲线（SUCRA）下的表面。我们主要使用标准化平均差（SMD）和95％置信区间（CI）报道了精子浓度和其他重要精液和生化结果。
结果：我们纳入了14项随机试验，评估了四种治疗方法（柠檬酸克罗米芬，他莫昔芬,芳香化酶抑制剂，抗氧化剂）及其在1342名男性中的组合。纳入试验的总体质量较低。与抗氧化剂相比，克罗米芬提高了精子浓度（SMD2.15，95CI0.78-3.52），芳香化酶抑制剂（SMD2.93，95CI1.23-4.62），他莫昔芬（SMD-1.96，95CI-3.57；-0.36），但与安慰剂（SMD-1.53，95CI-3.52-0.47）相比。克罗米芬具有最高的可能性来实现精子浓度的最大变化(SUCRA97.4)。所有的治疗方法对精子活力都有相似的作用,精液体积,精子形态正常.氯米芬与氯米芬的FSH水平显着改善。抗氧化剂（SMD1.48，95CI0.44-2.51），但与安慰剂相比。与其他治疗相比，克罗米芬和睾丸激素的证据网络存在显着不一致性（p=0.01），但与安慰剂相比，克罗米芬的改善趋势相似。
结论：没有足够的证据支持常规使用克罗米芬，他莫昔芬,和芳香化酶抑制剂，以优化不育男性的精液参数。未来的随机试验需要证实克罗米芬在改善男性生育结局方面的功效。
■CRD42023430179。
目的：我们旨在使用系统评价和网络荟萃分析比较非激素药物治疗方案对男性不孕症的有效性。
方法：我们搜索了MEDLINE，EMBASE,和CENTRAL，直到2023年10月进行随机/半随机试验，评估特发性精液异常或性腺功能减退男性的任何非激素药物治疗方案。我们使用随机效应模型进行了成对和网络荟萃分析。我们评估了偏见的风险，异质性，网络不一致。我们计算了每个干预措施实现每个报告结果的最大可能性的平均排名和累积排名曲线（SUCRA）下的表面。我们主要使用标准化平均差（SMD）和95％置信区间（CI）报道了精子浓度和其他重要精液和生化结果。
结果：我们纳入了14项随机试验，评估了四种治疗方法（柠檬酸克罗米芬，他莫昔芬,芳香化酶抑制剂，抗氧化剂）及其在1342名男性中的组合。纳入试验的总体质量较低。与抗氧化剂相比，克罗米芬提高了精子浓度（SMD2.15，95CI0.78-3.52），芳香化酶抑制剂（SMD2.93，95CI1.23-4.62），他莫昔芬（SMD-1.96，95CI-3.57；-0.36），但与安慰剂（SMD-1.53，95CI-3.52-0.47）相比。克罗米芬具有最高的可能性来实现精子浓度的最大变化(SUCRA97.4)。所有的治疗方法对精子活力都有相似的作用,精液体积,精子形态正常.氯米芬与氯米芬的FSH水平显着改善。抗氧化剂（SMD1.48，95CI0.44-2.51），但与安慰剂相比。与其他治疗相比，克罗米芬和睾丸激素的证据网络存在显着不一致性（p=0.01），但与安慰剂相比，克罗米芬的改善趋势相似。
结论：没有足够的证据支持常规使用克罗米芬，他莫昔芬,和芳香化酶抑制剂，以优化不育男性的精液参数。未来的随机试验需要证实克罗米芬在改善男性生育结局方面的功效。
■CRD42023430179。
