激素辅助治疗对隐睾儿童睾丸生精功能影响的系统评价和Meta分析

Impact of the adjunctive hormonal therapy on testicular spermatogenic function among cryptorchid : a systematic review and meta-analysis

目的评价激素辅助治疗对于隐睾儿童睾丸生精功能的影响。方法计算机检索Pub Med、EMBASE、The Cochrane Library、中国生物医学文献数据库、中国知网、万方数据库和维普数据库,获得激素对隐睾儿童睾丸生精功能影响的干预性研究,检索时限均从建库至2015年9月30日。由2名研究者独立行文献筛选、资料提取,并评价纳入研究的偏倚风险。以睾丸固定术中睾丸活检每曲细精管横断面精原细胞数(S/T)为近期指标,以均数差(MD)及其95%CI作为效应指标;以成年后患者精子密度正常比例为远期指标,以相对危险度(RR)及其95%CI作为效应指标。采用Rev Man 5.3软件行Meta分析,根据异质性检验结果选择相应的效应模型合并效应量。结果 8篇文献进入Meta分析,4篇为RCT,4篇为NRCT。8篇文献的偏倚风险均较大。3篇文献报道了绒毛膜促性腺激素(h CG)+手术和单纯手术睾丸活检S/T水平,文献间具同质性,Meta分析结果显示,h CG+手术S/T水平显著低于单纯手术,MD=-0.08,95%CI:-0.13^-0.03,P=0.002。4篇文献汇总的随机效应模型Meta分析结果显示,促黄体生成素释放激素(LHRH)+手术S/T显著高于单纯手术,差异有统计学意义,MD=0.34,95%CI:0.04~0.64,P=0.03;按部位行亚组分析显示,单侧或双侧隐睾LHRH+手术均较单纯手术S/T显著增加。2篇文献汇总的随机效应模型Meta分析结果显示,h CG+LHRH+手术与单纯手术比较,成年后精子密度正常比例差异无统计学意义,RR=1.46,95%CI:0.24~9.06,P=0.68。结论 h CG辅助治疗对短期睾丸生精功能有损伤;LHRH辅助治疗可改善短期睾丸生精功能;而h CG+LHRH对于远期生精功能无显著影响。考虑纳入文献数量较少且偏倚风险高,仍有待更多的研究。

Objective To systematically evaluate the effect of hormonal therapy on testicular spermatogenic function of children with cryptorchidism. Methods Pub Med,EMBASE,The cochrane library,CBM,CNKI,Wan Fang Date and VIP were searched to collect relevant studies investigating the impact of hormonal therapy in the testicular spermatogenic function among cryptorchid. Two reviewers independently screened literatures,extracted data,and assessed the risk bias of included studies. As the short-term indicator,the spermatogonia per tubule（ S / T） was expressed as mean difference（ MD） and its 95% confidence intervals（ CI）. For the long-term indicator,the proportion of cryptorchidism who will have a normal sperm concentration in adulthood was expressed as risk ratio（ RR） with 95% CI. The meta-analysis was performed using Rev Man 5. 3 software. A fixed-effect model or a random-effect model would be used acording to the heterogeneity. Results A total of 4 RCTs（ n = 168） and 4 Non-randomized controlled trials（ NRCT）（ n = 248） were included. All of these studies had high risk of bias. Among them,3 studies reported the S/T of HCG ＋surgery group and surgery alone group,the fixed-effect model showed that h CG had decreased the S / T,MD =- 0. 08,95% CI：-0. 13 to- 0. 03）,P = 0. 002. Four studies was pooled in the meta-analysis using random-effect model. It showed that compared with surgery alone group,LHRH ＋ surgery group had increased S / T,MD = 0. 34,95% CI： 0. 04 to 0. 64,P = 0. 03,and subgroup analysis indicated the same effect in unilateral or bilateral cryptorchid. Compared with cryptorchid treated by surgery alone,the h CG ＋ LHRH ＋ surgery group did not increase the rate of sperm concentration with the normal range among patients who had history of cryptorchidism,RR = 1. 46,95% CI： 0. 24 to 9. 06,P = 0. 68. Conclusion Cryptorchid boys treated with h CG show damage in short-term testicular spermatogenic function,and LHRH would improve it. There is no evidence that combined usage of HCG ad LHRH will benefit long- term sperm concentration. Due to the limited quality and quantity of the included studies,more high quality studies are needed to verify the above conclusion.