肉碱治疗原发性弱精症疗效和安全性的系统评价

Carnitine in the Treatment of Idiopathic Asthenozoospermia:A Systematic Review

目的评价肉碱治疗原发性弱精症的疗效和安全性。方法采用Cochrane系统评价方法,电子检索1995年1月至2006年12月期间MEDLINE、EMbase、Cochrane图书馆、CNKI等资料库,辅以手工检索及追查已纳入文献的参考文献。纳入肉碱治疗原发性弱精症的随机对照试验(RCT)。由2名评价者共同评价纳入研究的质量,对符合标准的研究采用RevMan4.2.10软件进行Meta分析。结果共纳入5个RCT,其中B级2个,C级3个,包括346例患者,排除失访人数后实际纳入307例进行Meta分析。Meta分析结果显示:①肉碱治疗3～6个月后,治疗组与对照组患者配偶的自然妊娠率差异有统计学意义[RR=2.46,95%CI(1.12,5.43),P=0.03];②肉碱治疗3个月和6个月后治疗组与对照组前向活动精子数差异均无统计学意义[WMD=9.16,95%CI(0.14,18.18),P=0.05;WMD=5.28,95%CI(-4.45,15.01),P=0.29)];③肉碱治疗3个月和6个月后治疗组与对照组前向活动精子率差异均无统计学意义[WMD=14.56,95%CI(-4.49,33.61),P=0.13;WMD=7.34,95%CI(-5.93,20.61),P=0.28];④肉碱治疗3个月和6个月后治疗组与对照组活动精子数差异均无统计学意义[WMD=15.32,95%CI(-1.34,31.98),P=0.07;WMD=6.20,95%CI(-3.00,15.39),P=0.19];⑤肉碱治疗3个月和6个月后治疗组与对照组精子总活动率差异均无统计学意义[WMD=2.97,95%CI(-5.75,11.69),P=0.50;WMD=4.48,95%CI(-9.17,18.14),P=0.52];⑥肉碱治疗3个月和6个月后治疗组和对照组精液量差异均无统计学意义[WMD=-0.12,95%CI(-0.55,0.30),P=0.57;WMD=0.03,95%CI(-0.38,0.45),P=0.87];⑦肉碱治疗3个月和6个月后治疗组与对照组精子密度差异均无统计学意义[WMD=7.92,95%CI(-2.85,18.68),P=0.15;WMD=1.02,95%CI(-5.09,7.14),P=0.74]。有3个研究报告治疗期间均无严重不良反应发生。结论现有证据显示,肉碱治疗可提高原发性弱精症导致不育患者配偶的自然妊娠率,但不能改善精液分析的各项指标,无明显不良反应。由于本系统评价纳入文献的数量及质量有限,目前尚不能肯定肉碱治疗能够改善原发性弱精症导致不育患者的预后。建议进行大样本、设计良好、指标全面的临床随机对照试验,以提供更佳证据。

Objectives To assess the effectiveness and safety of carnitine in the treatment of idiopathic asthenozoospermia. Methods The Cochrane Library, MEDLINE, EMbase, and CNKI were searched between Jan 1995 and Dec 2006. Both English and Chinese studies were included in the review if they were randomized controlled trials （RCTs） involving men with idopathic asthenozoospermia who were treated with carnitine. Trial screening, data extraction, and quality assessment of included trials were conducted by method recommended by Cochrane Collaboration. Statistical analysis was conducted using RevMan 4.2.10 software. Results Five RCTs involving 346 patients met the inclusion criteria, and 307 patients were included in the meta-analysis. The results showed that： after being treated with carnitine for 3 and 6 months, the difference of the patients＇ partners＇ spontaneous pregnancy rate between treatment group and control group was statistically significant with RR2.46 and 95% CI 1.12 to 5.43 （Z=2.23, P=0.03）. After being treated with carnitine for 3 and 6 months, the difference of forward motile sperm per ejaculate between treatment group and control group was not statistically significant with WMD 9.16 and 95%CI 0.14 to 18.18 （Z=1.99, P=0.05） and WMD 5.28 and 95%CI -4.45 to 15.01 （Z=1.06, P=0.29）. After being treated with carnitine for 3 and 6 months, the difference of percentage of forward sperm motility between treatment group and control group was not statistically significant with WMD 14.56 and 95%CI M.49 to 33.61（ Z=1.50 ,P=0.13）, and WMD 7.34 and 95%CI-5.93 to 20.61 （Z=1.08, P=0.28）. After being treated with carnitine for 3 and 6 months, the difference of total motile sperm per ejaculate between treatment group and control group was not statistically significant with WMD 15.32 and 95%CI -1.34 to 31.98 （Z=1.80, P=0.07） and WMD 6.20, 95%CI -3.00 to 15.39 （Z= 1.32, P=0.19）.After being treated with carnitine for 3 and 6 months, the difference of percentage of total sperm motility between treatment group and control group was not statistically significant with WMD 2.97 and 95%CI-5.75 to 11.69 （Z=0.67, P=0.50） and WMD 4.48 and 95%CI-9.17 to18.14 （Z=0.64, P=0.52）. After being treated with carnitine for 3 and 6 months, the difference of semen volume between treatment group and control group was not statistically significant with WMD-0.12 and 95%CI-0.55 to 0.30 （Z=0.57, P=0.57） and WMD 0.03 and 95%CI -0.38 to 0.45 （Z=0.16, P=0.87）. After being treated with carnitine for 3 and 6 months, the difference of sperm concentration between treatment group and control group was not statistically significant with WMD 7.92 and 95%CI -2.85 to18.68 （Z=1.44, P=0.15）, and WMD 1.02 and 95%CI -5.09 to 7.14 （Z=0.33, P=0.74）. Three RCTs reported that there were no serious side effects of carnitine during the treatment period. Conclusions The available evidence indicates that spontaneous pregnancy rate would increase with carnitine therapy, while it is short of improvement of semen parameters. There is no serious side effect of carnitine. Because of lack of evidence, we cannot conclude that carnitine is effective in improving the prognosis of infertile patients with idiopathic asthenozoospermia. More high quality trials with large sample are proposed.