張 驌 王 誠(chéng) 付生軍 楊 立

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·論著·

激素輔助治療對(duì)隱睪兒童睪丸生精功能影響的系統(tǒng)評(píng)價(jià)和Meta分析

張 驌 王 誠(chéng) 付生軍 楊 立

目的 評(píng)價(jià)激素輔助治療對(duì)于隱睪兒童睪丸生精功能的影響。方法 計(jì)算機(jī)檢索PubMed、EMBASE、The Cochrane Library、中國(guó)生物醫(yī)學(xué)文獻(xiàn)數(shù)據(jù)庫、中國(guó)知網(wǎng)、萬方數(shù)據(jù)庫和維普數(shù)據(jù)庫，獲得激素對(duì)隱睪兒童睪丸生精功能影響的干預(yù)性研究，檢索時(shí)限均從建庫至2015年9月30日。由2名研究者獨(dú)立行文獻(xiàn)篩選、資料提取，并評(píng)價(jià)納入研究的偏倚風(fēng)險(xiǎn)。以睪丸固定術(shù)中睪丸活檢每曲細(xì)精管橫斷面精原細(xì)胞數(shù)(S/T)為近期指標(biāo)，以均數(shù)差(MD)及其95%CI作為效應(yīng)指標(biāo)；以成年后患者精子密度正常比例為遠(yuǎn)期指標(biāo)，以相對(duì)危險(xiǎn)度(RR)及其95%CI作為效應(yīng)指標(biāo)。采用RevMan 5.3軟件行Meta分析，根據(jù)異質(zhì)性檢驗(yàn)結(jié)果選擇相應(yīng)的效應(yīng)模型合并效應(yīng)量。結(jié)果 8篇文獻(xiàn)進(jìn)入Meta分析，4篇為RCT，4篇為NRCT。8篇文獻(xiàn)的偏倚風(fēng)險(xiǎn)均較大。3篇文獻(xiàn)報(bào)道了絨毛膜促性腺激素(hCG)+手術(shù)和單純手術(shù)睪丸活檢S/T水平，文獻(xiàn)間具同質(zhì)性，Meta分析結(jié)果顯示，hCG+手術(shù)S/T水平顯著低于單純手術(shù)， MD=-0.08,95%CI：-0.13～-0.03,P=0.002。4篇文獻(xiàn)匯總的隨機(jī)效應(yīng)模型Meta分析結(jié)果顯示，促黃體生成素釋放激素(LHRH)+手術(shù)S/T顯著高于單純手術(shù)，差異有統(tǒng)計(jì)學(xué)意義，MD=0.34，95%CI：0.04～0.64,P=0.03；按部位行亞組分析顯示，單側(cè)或雙側(cè)隱睪LHRH+手術(shù)均較單純手術(shù)S/T顯著增加。2篇文獻(xiàn)匯總的隨機(jī)效應(yīng)模型Meta分析結(jié)果顯示， hCG+LHRH+手術(shù)與單純手術(shù)比較，成年后精子密度正常比例差異無統(tǒng)計(jì)學(xué)意義，RR=1.46,95%CI：0.24～9.06,P=0.68。 結(jié)論 hCG輔助治療對(duì)短期睪丸生精功能有損傷；LHRH輔助治療可改善短期睪丸生精功能；而hCG+LHRH對(duì)于遠(yuǎn)期生精功能無顯著影響?？紤]納入文獻(xiàn)數(shù)量較少且偏倚風(fēng)險(xiǎn)高，仍有待更多的研究。

隱睪； 絨毛膜促性腺激素； 促黃體生成素釋放激素； 生精功能； Meta分析 系統(tǒng)評(píng)價(jià)

隱睪病因尚不清楚，其遠(yuǎn)期預(yù)后主要包括生育能力和睪丸惡變，故早期如何進(jìn)行有效的治療是臨床關(guān)注的熱點(diǎn)。有研究顯示隱睪手術(shù)治療成功率約為70%，且并發(fā)癥少，而激素輔助治療的成功率約為20%，且不良事件發(fā)生率較高[1, 2]。2014年美國(guó)泌尿外科指南推薦首選手術(shù)治療隱睪，不推薦激素治療，主要考慮激素治療的睪丸下降率低，且有較多不良反應(yīng)，尤其可引起精原細(xì)胞損傷[3]。北歐國(guó)家也不建議激素治療，推薦在6～12月齡行手術(shù)干預(yù)[4]。但早期手術(shù)干預(yù)并未明顯改善生育能力及睪丸惡變率[5]。激素輔助治療包括睪丸固定術(shù)前或術(shù)后應(yīng)用絨毛膜促性腺激素(hCG)或促黃體激素釋放激素(LHRH)。研究顯示hCG可增加睪丸體積，促進(jìn)睪丸血供，舒張?zhí)岵G??；但有研究顯示hCG可損害睪丸組織[6,7]。近期有前瞻性研究顯示LHRH輔助治療可促進(jìn)睪丸發(fā)育及生精功能，如增加睪丸活檢每曲細(xì)精管橫斷面精原細(xì)胞數(shù)(S/T)，且不良反應(yīng)小[8, 9]。而S/T與成年后生育能力呈顯著正相關(guān)[10]。2014版的歐洲泌尿外科指南并不反對(duì)激素輔助治療，并指出現(xiàn)有對(duì)于激素治療隱睪的反對(duì)意見主要來自hCG可能損傷睪丸生精功能的相關(guān)研究，并非針對(duì)LHRH。為此本研究檢索相關(guān)文獻(xiàn)，對(duì)不同激素輔助療法對(duì)隱睪患兒睪丸生精功能影響行定量評(píng)價(jià)，以期為激素輔助治療隱睪提供依據(jù)。

1 方法

1.1 文獻(xiàn)納入標(biāo)準(zhǔn) ①干預(yù)類研究，包括RCT和NRCT；②單側(cè)及雙側(cè)隱睪，種族不限；③干預(yù)措施為激素(單用hCG、單用LHRH、hCG+LHRH)加手術(shù)治療，對(duì)照為單純手術(shù)治療；④報(bào)道了本文設(shè)定的結(jié)局指標(biāo)。

1.2 文獻(xiàn)排除標(biāo)準(zhǔn) ①回縮性隱睪；②合并疝氣；③二次手術(shù)者；④睪丸缺如；⑤兩性畸形或其他染色體疾?。虎拗貜?fù)發(fā)表的文獻(xiàn)；⑦原始研究結(jié)局?jǐn)?shù)據(jù)報(bào)告不全，與作者聯(lián)系后無法獲得所需數(shù)據(jù)的文獻(xiàn)。

1.3 結(jié)局指標(biāo) 近期指標(biāo) ：睪丸固定術(shù)中睪丸活檢S/T。遠(yuǎn)期指標(biāo)：成年后精子密度正常比例，參考WHO第4版《人類精液和精子-宮頸黏液相互作用實(shí)驗(yàn)室檢驗(yàn)手冊(cè)》，正常值>20×106·mL-1。

1.4 文獻(xiàn)檢索策略 計(jì)算機(jī)檢索PubMed、EMBASE、The Cochrane Library、中國(guó)生物醫(yī)學(xué)文獻(xiàn)數(shù)據(jù)庫、中國(guó)知網(wǎng)、萬方數(shù)據(jù)庫和維普數(shù)據(jù)庫，檢索時(shí)限均從建庫至2015年9月30日。

英文檢索詞：Cryptorchidism、Undescended testis、Gonadotropin releasing hormone、Luteinizing hormone-releasing hormone、GnRH、LHRH、Chorionic gonadotropin、Human chorionic gonadotropin、hCG。

以PubMed數(shù)據(jù)庫為例，其具體檢索策略如下。

#1 "Cryptorchidism"[MeSH Terms] OR "Undescended testis"[Title/Abstract] OR "Undescended testes"[Title/Abstract] OR Cryptorchidism[Title/Abstract] OR Cryptorchism[Title/Abstract]

#2 "Gonadotropin-releasing hormone"[MeSH Terms] OR "Gonadotropin releasing hormone"[Title/Abstract] OR GnRH[Title/Abstract]) OR Buserelin[Title/Abstract]) OR LHRH[Title/Abstract] OR Gonadotropin-releasing hormone[Title/Abstract]

#3 "Chorionic gonadotropin"[MeSH Terms] OR Choriogonadotropin[Title/Abstract]) OR Choriogonin[Title/Abstract] OR Pregnyl[Title/Abstract] OR Chorulon[Title/Abstract] OR Gonabion[Title/Abstract] OR "Human chorionic gonadotropin"[Title/Abstract] OR "Chorionic gonadotropin, Human"[Title/Abstract]) OR HCG[Title/Abstract]) OR hCG[Title/Abstract] OR "Chorionic gonadotropin"[Title/Abstract]

#4 #1 AND ( #2 OR #3)

中文檢索詞：隱睪、未下降睪丸、HCG、激素、LHRH、促性腺激素釋放激素、人絨毛膜促性腺激、GnRH、促黃體激素釋放激素。

1.5 文獻(xiàn)篩選、資料提取和偏倚風(fēng)險(xiǎn)評(píng)價(jià) 由張驌與王誠(chéng)獨(dú)立進(jìn)行，并交叉核對(duì)，如遇分歧，由付生軍裁決。提取資料包括：①文獻(xiàn)基本信息，第一作者、發(fā)表年份和國(guó)家；②研究對(duì)象基本特征：激素種類及用法、各組病例數(shù)、患者年齡和手術(shù)年齡；③RCT或NRCT及其偏倚風(fēng)險(xiǎn)評(píng)價(jià)內(nèi)容；④結(jié)局指標(biāo)。RCT文獻(xiàn)的偏倚風(fēng)險(xiǎn)采用Cochrane系統(tǒng)評(píng)價(jià)員手冊(cè)推薦的6條標(biāo)準(zhǔn)評(píng)價(jià)，以是、否和不清楚表示；NRCT的偏倚風(fēng)險(xiǎn)采用MINORS量表(Methodological index for non-randomized studies)評(píng)價(jià)，共包含12個(gè)條目。每個(gè)條目未報(bào)道賦0分，有報(bào)道但信息不充分賦1分，有報(bào)道且信息充分賦2分。

1.6 統(tǒng)計(jì)學(xué)方法 采用RevMan 5.3軟件行Meta分析。計(jì)數(shù)資料以相對(duì)危險(xiǎn)度(RR)、計(jì)量資料以均數(shù)差(MD)及其95%CI作為效應(yīng)指標(biāo)。 首先采用χ2檢驗(yàn)行各研究結(jié)果間的異質(zhì)性分析，若各文獻(xiàn)間P>0.1，I2<50%，采用固定效應(yīng)模型合并結(jié)果；若各文獻(xiàn)間P<0.1，I2>50%，則進(jìn)一步分析異質(zhì)性來源，在排除明顯臨床異質(zhì)性的影響后，采用隨機(jī)效應(yīng)模型行Meta分析。若各研究間存在明顯臨床異質(zhì)性，采用亞組分析或敏感性分析。P<0.05 為差異有統(tǒng)計(jì)學(xué)意義。

2 結(jié)果

2.1 文獻(xiàn)檢索結(jié)果 初步檢索共獲得相關(guān)文獻(xiàn)1 988篇， 8篇文獻(xiàn)[9,11～17]進(jìn)入Meta分析(圖1)，4篇RCT(n=187)，4篇NRCT (n=248)。納入文獻(xiàn)的基本特征如表1所示。

圖1 文獻(xiàn)篩選流程圖

Fig 1 Flow chart of aricle screening and selection process

2.2 偏倚風(fēng)險(xiǎn)評(píng)價(jià) 4篇RCT文獻(xiàn)[9,12,15,17]隨機(jī)序列的產(chǎn)生和分配隱藏均不清楚，均未對(duì)受試者和研究者施盲，對(duì)結(jié)局測(cè)量均采用盲法，均未選擇性報(bào)告研究結(jié)果，結(jié)果數(shù)據(jù)均具完整性，其他偏倚來源為不清楚。4篇NRCT文獻(xiàn)[11,13,14,16]均報(bào)道了研究目的、數(shù)據(jù)收集、終點(diǎn)指標(biāo)的選擇與評(píng)價(jià)、失訪率、對(duì)照組的選擇、組間基線可比性與統(tǒng)計(jì)分析，且信息充分；文獻(xiàn)[11,13]報(bào)道了納入病例的連續(xù)性，但信息不充分，文獻(xiàn)[14,16]未報(bào)道；文獻(xiàn)[11,13]報(bào)道了隨訪時(shí)間且信息充分，文獻(xiàn)[14,16]未報(bào)道；文獻(xiàn)[11]報(bào)道了對(duì)照組與試驗(yàn)組同期進(jìn)行的同步性且信息充分，文獻(xiàn)[13]提供的信息不充分，文獻(xiàn)[14,16]未報(bào)道；4篇文獻(xiàn)均未報(bào)道樣本量的估算。文獻(xiàn)[11]評(píng)為20分，文獻(xiàn)[13,14,16]評(píng)為18分。

2.3 Meta分析結(jié)果

2.3.1 睪丸活檢S/T 3篇文獻(xiàn)比較了hCG+手術(shù)和單純手術(shù)的睪丸活檢S/T，共納入175例患兒。文獻(xiàn)間具同質(zhì)性，固定效應(yīng)模型Meta分析顯示： hCG+手術(shù)的S/T低于單純手術(shù)，差異有統(tǒng)計(jì)學(xué)意義，MD=-0.08,95%CI:-0.13～-0.03,P=0.002(圖2)。

4篇文獻(xiàn)比較了LHRH+手術(shù)和單純手術(shù)的睪丸活檢S/T，共納入344例患兒。異質(zhì)性檢驗(yàn)I2=83%，P<0.000 1，采用隨機(jī)效應(yīng)模型進(jìn)行合并，Meta分析顯示，LHRH+手術(shù)睪丸活檢S/T高于單純手術(shù)，差異有統(tǒng)計(jì)學(xué)意義，MD=0.34，95%CI:0.04～0.64,P=0.03。按部位行亞組分析，單側(cè)隱睪：LHRH+手術(shù)較單純手術(shù)S/T增加，MD=0.43，95%CI：0.21～0.65,P=0.000 2；雙側(cè)隱睪，LHRH+手術(shù)較單純手術(shù)S/T增加，MD=0.43，95%CI：0.17～0.68,P=0.001(圖3)。

2.3.2 正常精子密度比例 文獻(xiàn)[14,16]文獻(xiàn)報(bào)道了成年后精液分析正常精子密度比例，文獻(xiàn)間P<0.000 1,I2=94%，隨機(jī)效應(yīng)模型Meta分析顯示：hCG+LHRH+手術(shù)和單純手術(shù)成年后正常精子密度比例差異無統(tǒng)計(jì)學(xué)意義，RR=1.46, 95%CI：0.24～9.06,P=0.68(圖4)。

圖2 HCG+手術(shù)和單純手術(shù)睪丸活檢S/T比較的Meta分析

圖3 LHRH+手術(shù)和單純手術(shù)睪丸活檢S/T比較的Meta分析

圖4 成年后精液分析正常精子密度比例的Meta分析

Fig 4 Meta-analysis of the rate of normal sperm concentration in adulthood

3 討論

本系統(tǒng)評(píng)價(jià)共納入8篇原始研究，其中包含4篇RCT與4篇NRCT。4篇RCT的隨機(jī)序列產(chǎn)生和分配隱藏均不清楚，均未對(duì)受試者和研究者施盲，具有較高的偏倚風(fēng)險(xiǎn)；4篇NRCT文獻(xiàn)MINORS得分在18～20分，雖無較高的偏倚風(fēng)險(xiǎn)，但對(duì)于干預(yù)性研究的論證強(qiáng)度較RCT低。本文Meta分析的證據(jù)強(qiáng)度較低。

hCG自從1930年應(yīng)用于隱睪治療，但治療效果仍存在爭(zhēng)議[18]。hCG治療隱睪的理論基礎(chǔ)是其可刺激睪丸間質(zhì)細(xì)胞而增加睪酮的產(chǎn)生。hCG治療隱睪有效率約25%[2]。術(shù)前應(yīng)用hCG，可增加睪丸血流，減少術(shù)中睪丸缺血[19]。隱睪患兒予hCG治療，成年后睪丸體積明顯大于未用藥組[6]。但hCG治療可引起睪丸的相關(guān)損傷，可引起睪丸間質(zhì)水腫、炎癥反應(yīng)、精原細(xì)胞凋亡、陰莖異常勃起以及遠(yuǎn)期抑制睪丸發(fā)育等[7, 13, 18, 20, 21]。本文Meta分析結(jié)果顯示，hCG+手術(shù)組較單純手術(shù)組S/T降低，提示hCG對(duì)睪丸生精功能造成了一定程度的損傷。

LHRH 及其類似物是下丘腦產(chǎn)生的促垂體分泌促黃體生成素的激素，可以增高血清中的促黃體生成激素水平，也可刺激睪丸間質(zhì)細(xì)胞使局部產(chǎn)生高濃度睪酮，且無特殊不良反應(yīng)，偶有陰莖異常勃起，但發(fā)生率明顯低于hCG治療組(5.1%vs74.1%)[18]。早期對(duì)照研究顯示，對(duì)hCG治療失敗的患兒行睪丸固定術(shù)，術(shù)后輔助應(yīng)用LHRH，成年后精液分析精子密度、活動(dòng)力以及形態(tài)都明顯優(yōu)于早年單純手術(shù)患兒[22]。近期RCT顯示，睪丸固定術(shù)前和術(shù)后4周應(yīng)用LHRH，隨訪5年，發(fā)現(xiàn)用藥組睪丸體積明顯大于未用藥組[8]。本文Meta分析結(jié)果顯示，LHRH+手術(shù)較單純手術(shù)治療，無論是單側(cè)隱睪，抑或雙側(cè)隱睪，S/T均增高，提示對(duì)睪丸生精功能有促進(jìn)作用。

本文Meta分析結(jié)果顯示，與單純手術(shù)相比，hCG+LHRH+手術(shù)未顯著增加患者成年后正常精子密度比例。且文獻(xiàn)[14] 與[16]分別顯示精子活動(dòng)力以及形態(tài)兩組間也無差異。但無法鑒別是否hCG的應(yīng)用降低了LHRH的促睪丸生精作用，還是兩者對(duì)睪丸生精功能的影響只是短期效應(yīng)，因有研究報(bào)道術(shù)前應(yīng)用hCG，停藥數(shù)周后行手術(shù)，未發(fā)現(xiàn)睪丸損傷[20,23]。

本研究的局限性：①納入文獻(xiàn)對(duì)于隱睪患兒手術(shù)治療時(shí)間的把握不同，可能會(huì)對(duì)結(jié)局的評(píng)價(jià)帶來影響；②各研究的藥物用量及用法不一致。

當(dāng)前證據(jù)顯示， hCG輔助治療對(duì)于短期睪丸生精功能有損害；LHRH輔助治療可改善短期睪丸生精功能；而hCG+LHRH作為輔助療法與單純手術(shù)治療隱睪對(duì)于遠(yuǎn)期生精功能無顯著影響?？紤]到納入文獻(xiàn)數(shù)量較少且偏倚風(fēng)險(xiǎn)較高，仍有待更多的研究。

[1]Penson D, Krishnaswami S, Jules A, et al. Effectiveness of hormonal and surgical therapies for cryptorchidism: a systematic review. Pediatrics, 2013, 131(6): 1897-1907

[2]Henna MR, Del Nero RG, Sampaio CZ, et al. Hormonal cryptorchidism therapy: systematic review with meta-analysis of randomized clinical trials. Pediatr Surg Int, 2004, 20(5): 357-359

[3]Kolon TF, Herndon CD, Baker LA, et al. Evaluation and treatment of cryptorchidism: AUA guideline. J Urol, 2014, 192(2): 337-345

[4]Ritzen EM, Bergh A, Bjerknes R, et al. Nordic consensus on treatment of undescended testes. Acta Paediatr, 2007, 96(5): 638-643

[5]Hutson JM, Balic A, Nation T, et al. Cryptorchidism. Semin Pediatr Surg, 2010, 19(3): 215-224

[6]Varela-Cives R, Mendez-Gallart R, Estevez-Martinez E, et al. A cross-sectional study of cryptorchidism in children: testicular volume and hormonal function at 18 years of age. Int Braz J Urol, 2015, 41(1): 57-66

[7]Dunkel L, Taskinen S, Hovatta O, et al. Germ cell apoptosis after treatment of cryptorchidism with human chorionic gonadotropin is associated with impaired reproductive function in the adult. J Clin Invest, 1997, 100(9): 2341-2346

[8]Spinelli C, Strambi S, Busetto M, et al. Effects on normalized testicular atrophy index (TAIn) in cryptorchid infants treated with GnRHa pre and post-operative vs surgery alone: a prospective randomized trial and long-term follow-up on 62 cases. Pediatr Surg Int, 2014, 30(10): 1061-1067

[9]Jallouli M, Rebai T, Abid N, et al. Neoadjuvant gonadotropin-releasing hormone therapy before surgery and effect on fertility index in unilateral undescended testes: a prospective randomized trial. Urology, 2009, 73(6): 1251-1254

[10]Hadziselimovic F, Herzog B. The importance of both an early orchidopexy and germ cell maturation for fertility. Lancet, 2001, 358(9288): 1156-1157

[11]Hadziselimovic F, Huff D, Duckett J, et al. Treatment of cryptorchidism with low doses of buserelin over a 6-months period. Eur J Pediatr, 1987, 146(S2):56-58

[12]Bica DT, Hadziselimovic F. Buserelin treatment of cryptorchidism: a randomized, double-blind, placebo-controlled study. J Urol, 1992, 148(2 Pt 2): 617-621

[13]Cortes D, Thorup J, Visfeldt J. Hormonal treatment may harm the germ cells in 1 to 3-year-old boys with cryptorchidism. J Urol, 2000, 163(4): 1290-1292

[14]Vinardi S, Magro P, Manenti M, et al. Testicular function in men treated in childhood for undescended testes. J Pediatr Surg, 2001, 36(2): 385-388

[15]Schwentner C, Oswald J, Kreczy A, et al. Neoadjuvant gonadotropin-releasing hormone therapy before surgery may improve the fertility index in undescended testes: a prospective randomized trial. J Urol, 2005, 173(3): 974-977

[16]Hadziselimovic F. Successful treatment of unilateral cryptorchid boys risking infertility with LH-RH analogue. Int Braz J Urol, 2008, 34(3): 319-326

[17]Zhao GJ(趙國(guó)進(jìn))，Su XG，Wu DG. The effect of human chorionic gonadotropin on the germ cells in patients with cryptorchidism. Heibei Medicine(河北醫(yī)學(xué)), 2011, 17(3): 319-321

[18]Bertelloni S, Baroncelli GI, Ghirri P, et al. Hormonal treatment for unilateral inguinal testis: comparison of four different treatments. Horm Res, 2001, 55(5): 236-239

[19]Geesaman B, Villanueva-Meyer J, Bluestein D, et al. Effects of multiple injections of HCG on testis blood flow. Urology, 1992, 40(1): 81-83

[20]Heiskanen P, Billig H, Toppari J, et al. Apoptotic cell death in the normal and cryptorchid human testis: the effect of human chorionic gonadotropin on testicular cell survival. Pediatr Res, 1996, 40(2): 351-356

[21]Taskinen S, Wikstrom S. Effect of age at operation, location of testis and preoperative hormonal treatment on testicular growth after cryptorchidism. J Urol, 1997, 158(2): 471-473

[22]Hadziselimovic F, Herzog B. Treatment with a luteinizing hormone-releasing hormone analogue after successful orchiopexy markedly improves the chance of fertility later in life. J Urol, 1997, 158(3 Pt 2): 1193-1195

[23]Demirbilek S, Atayurt HF, Celik N, et al. Does treatment with human chorionic gonadotropin induce reversible changes in undescended testes in boys? Pediatr Surg Int, 1997, 12(8): 591-594

(本文編輯：丁俊杰)

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

ZHANGSu,WANGCheng,FUSheng-jun,YANGLi

(DepartmentofUrology,theSecondHospitalofLanzhouUniversity,InstituteofUrologyofLanzhouUniversity,KeyLaboratoryofDiseasesofUrologicalSysteminGansuProvince,GansuNephron-UrologicalClinicalCenter,Lanzhou730030,China)

YANG Li，E-mail:yuze250@163.com

ObjectiveTo systematically evaluate the effect of hormonal therapy on testicular spermatogenic function of children with cryptorchidism.MethodsPubMed, EMBASE, The cochrane library, CBM, CNKI, WanFang 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 RevMan 5.3 software.A fixed-effect model or a random-effect model would be used acording to the heterogeneity.ResultsA 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 hCG 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 hCG+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. ConclusionCryptorchid boys treated with hCG 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.

Cryptorchidism; Human chorionic gonadotropin; Luteinizing hormone releasing hormone; Spermatogenic function; Meta-analysis; Systematic review

蘭州大學(xué)泌尿外科研究所，蘭州大學(xué)第二醫(yī)院泌尿外科 甘肅省泌尿系統(tǒng)疾病臨床醫(yī)學(xué)中心，甘肅省泌尿系統(tǒng)疾病研究重點(diǎn)實(shí)驗(yàn)室 蘭州，730030

楊立，E-mail:yuze250@163.com

10.3969/j.issn.1673-5501.2015.06.008

2015-09-17

2015-12-03)