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中华妇幼临床医学杂志(电子版) ›› 2013, Vol. 09 ›› Issue (03) : 287 -294. doi: 10.3877/cma.j.issn.1673-5250.2013.03.004

所属专题： 文献；

论著

两种降调节方案对体外受精胚胎移植中子宫内膜异位症不孕患者有效性的Meta分析
董兰1, 徐望明1,*,*(), 罗增丽1, 周小燕1, 王慧明1   
  1. 1. 430060　武汉，武汉大学人民医院生殖中心
  • 收稿日期:2013-02-22 修回日期:2013-03-31 出版日期:2013-06-01
  • 通信作者: 徐望明

Effectiveness of in Vitro Fertilization Embryo Transfer Conducted With Two Kinds of Down Regulation Protocols on Infertile Patients With Endometriosis: A Meta Analysis

Lan DONG1, Wang-ming XU1(), Zeng-li LUO1, Xiao-yan ZOU1, Hui-ming WANG1   

  1. 1. Reproduction Center, Renmin Hospital of Wuhan University, Hubei 430060, Hubei Province, China
  • Received:2013-02-22 Revised:2013-03-31 Published:2013-06-01
  • Corresponding author: Wang-ming XU
  • About author:
    (Corresponding author: XU Wang-ming, Email: )
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引用本文：

董兰, 徐望明, 罗增丽, 周小燕, 王慧明. 两种降调节方案对体外受精胚胎移植中子宫内膜异位症不孕患者有效性的Meta分析[J]. 中华妇幼临床医学杂志(电子版), 2013, 09(03): 287-294.

Lan DONG, Wang-ming XU, Zeng-li LUO, Xiao-yan ZOU, Hui-ming WANG. Effectiveness of in Vitro Fertilization Embryo Transfer Conducted With Two Kinds of Down Regulation Protocols on Infertile Patients With Endometriosis: A Meta Analysis[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2013, 09(03): 287-294.

目的

系统评价超长方案和长方案降调节在体外受精胚胎移植(IVF-ET)子宫内膜异位症(EMs)不孕患者治疗中的有效性。

方法

计算机检索2000年1月至2012年6月中国生物医学文献数据库(CBMDisc)、万方数据库、中国学术期刊网专题全文数据库(CNKI)、维普数据库、Pubmed、外文生物医学期刊文献数据(FMJS)中有关超长方案和长方案应用促性腺激素(Gn)降调节在对IVF-ET的EMs不孕患者治疗中的有效性的随机对照试验(RCT)，同时检索纳入文献的参考文献。对纳入研究文献的质量，由3位研究者共同评价，对同质研究进行Meta分析。统计学分析采用RevmMan 5.1软件。

结果

文献检索结果为7篇文献符合本研究纳入标准，涉及受试者为593例，将其中采取超长方案降调受试者纳入超长方案组(n＝219)，长方案降调的受试者纳入长方案组(n＝374)。对其进行Meta分析的结果显示：两组的周期取消率比较，差异无统计学意义(WMD＝0.69，95%CI：0.32～1.51；P＝0.35)；两组IVF-ET中，应用促性腺激素释放激素激动剂(GnRHa)刺激的时间比较，差异无统计学意义(WMD＝0.12，95%CI：－0.04～0.28；P＝0.14)；超长方案组应用Gn总剂量高于长方案组，且差异有统计学意义(WMD＝311.25，95%CI：6.43～616.08；P＝0.05)；两组获卵数比较，差异无统计学意义(WMD＝－0.65，95%CI：－1.76～0.47；P＝0.25)；两组人绒毛膜促性腺激素(hCG)日血清雌激素(E2)水平比较，差异无统计学意义(WMD＝－499.71，95% CI：－1171.02～171.60；P＝0.14)；临床妊娠率比较超长方案组较长方案组高，且差异有统计学意义(WMD＝2.23，95%CI：1.49～3.33；P<0.0001)；两组自然流产率比较，差异无统计学意义(WMD＝1.31，95%CI：0.37～4.64；P＝0.68)。

结论

EMs导致的不孕患者在IVF-ET治疗中，超长方案较长方案可显著提高临床妊娠率。对EMs导致的不孕患者行IVF-ET可能是较理想的选择。鉴于本研究纳入文献存在质量和样本数量不足及方法学差异，上述结论仅供临床参考，对超长方案和长方案降调节在对IVF-ET的EMs不孕患者治疗的有效性，尚需开展更多后效评价和不断更新。

关键词: 子宫内膜异位症, 体外受精-胚胎移植, 超长方案, 长方案, Meta分析
Objective

To evaluate the effectiveness of two kinds of down regulation protocols used in vitro fertilization embryo transfer( IVF-ET) in infertile patients with endometriosis(EMs).

Methods

CBM disc, Wan fang, CNKI, VIP, Pubmed, PML, FMJS were searched for randomized controlled trails(RCTs) on the comparison between prolonged protocol and long protocol in IVF-ET in infertility patients with EMs. The bibliography of the included studies were searched, too. The duration of search was form January 2000 to June 2012.The quality of the included was evaluated by three evaluators. For the homogeneous studies we performed Meta analysis. The extracted data were analyzed by RenMan 5.1.

Results

Seven literatures with 593 participants were selected for Meta analysis based on our including standards. Which involving 219 cases with prolonged protocol and 374 cases with long protocol of gonadotrophins(Gn). Meta analyses showed that prolonged protocol compared with long protocol cancellation rates were no significant difference in two groups at WMD=0.69 and 95%CI: 0.32-1.51; gonadotrophin releasing hormone analogue(GnRHa) stimulation durations were no significant difference in two groups at WMD=0.12 and 95% CI: -0.04-0.28; doses of GnRHa in prolonged protocol group were higher at the WMD=-311.25 and 95%CI: 6.43-616.08, the differences were statistically significant; the number of oocytes retrieved was no significant difference between two group at the WMD=-0.65 and 95%CI: -1.76-0.47(P>0.05); the differences were statistically significant serum E2 levels on the day of human chorionic gonadotrophin(hCG) administration was no significant difference in two groups at the WMD=-499.71 and 95%CI: -1171.02-171.60(P>0.05); clinical pregnancy rates in prolonged protocol group were slightly higher at the WMD=2.23 and 95%CI: 1.49-3.33, the differences were statistically significant(P<0.05); spontaneous abortion rates were no significant difference in two groups at the WMD=1.31 and 95% CI: 0.37-4.64(P>0.05).

Conclusions

In EMs patients with infertility IVF-ET treatment, compared with long protocol, the prolonged protocol can obviously increase the clinical pregnancy rate, so the IVF-ET may be an ideal choice for EMs patients with infertility. Because the including trails exist insufficiency on quality and quantity as well as the methodology difference, suggested that this research conclusion only serve as the reference of the clinical analysis, need reevaluation and renew unceasingly.

Key words: endometriosis, in vitro fertilization embryo transfer, prolonged/ultralong protocol, long protocol, Mate analysis
表1 纳入研究的7篇文献的特性(±s)
Table 1 Characteristics among 7 literatures included in the study(±s)
纳入文献(第一作者/发表年代) n 受试者年龄(岁) 不孕时间(年) 基础FSH(IU/L) E2(pg/mL)
超长方案组 长方案组 超长方案组 长方案组 超长方案组 长方案组 超长方案组 长方案组 超长方案组 长方案组
Surrey ES/2002[4] 25 26 33.12± 0.67 32.58± 0.56 － － 6.17±0.54 30.26±5.37 30.26± 5.37 30.23± 4.84
Rickes D/2002[5] 28 19 23.00～40.00 23.00～40.00 － － <12 <12 － －
牛海燕/2011[6] 25 25 31.50± 2.5 32.10± 2.70 5.60±2.80 5.50±3.10 7.00±2.10 6.90±2.60 45.20± 8.70 46.10± 7.90
孟晓华/2006[7] 18 24 31.11± 0.74 30.96± 0.75 4.46±0.57 4.18±0.52 3.85±0.42 4.36±0.40 41.35± 2.13 39.72± 2.76
邓华丽/2012[8] 74 177 30.84± 2.67 30.49± 3.11 5.77±3.36 5.61±3.32 3.86±2.81 3.32±1.19 33.00±14.10 31.73±14.98
林文琴/2004[9] 26 36 31.00± 4.00 32.00± 3.00 5.00±4.00 6.00±5.00 6.90±1.90 7.10±2.00 － －
程丹/2010[10] 23 67 31.70± 4.10 31.30± 3.50 5.50±3.30 5.10±2.70 7.00±2.30 6.90±2.70 49.80±12.60 56.80±14.80
纳入文献(第一作者/发表年代) AFS分期 治疗方法 结局指标包括
Ⅰ～Ⅱ Ⅲ～Ⅳ 超长方案组 长方案组
Surrey ES/2002[4] 15 36 卵泡早期采用醋酸亮丙瑞林1次/28 d，共3支，第3支用后的50 d内，每天采用Gn促排卵至hCG日 黄体中期应用醋酸亮丙瑞林(0.5～1.0) mg/d，应用(7～10)d，促排卵至hCG日 ②③④⑥
Rickes D/2002[5] 15 32 皮下注射戈舍瑞林，1次/28 d，共5～6支，降调满意后，Gn促排卵至hCG日 月经第18天，皮下注射曲普瑞林0.1 mg/d，转经后第3天，促排卵至hCG日 ⑥
牛海燕/2011[6] － 50 月经第2天皮下注射曲普瑞林1次/28 d，共2～3支，降调节满意后，Gn促卵排至hCG日 月经第21天皮下注射曲普瑞林0.1 mg/d至月经来潮，然后减量为0.05 mg/d，并Gn超促排卵至hCG日 ③④
孟晓华/2006[7] － 42 月经周期第1天皮下注射戈舍瑞林3.6 mg，1次/28 d，共3支，末次注射后(28～30)d，Gn促排卵至hCG日 于基础体温上升第6～7天，予皮下注射曲普瑞林0.1 mg/d，转经第3天，Gn促排卵至hCG日 ②③④⑤⑥
邓华丽/2012[8] 140 111 月经周期第1天皮下注射长效曲普瑞林3.75 mg，1次/28 d，共3支，第3支后(28～50)d，Gn促排卵至hCG日 标准黄体期长方案：黄体中期皮下注射曲普瑞林0.1 mg/d，降调节满意后，Gn促排卵至hCG日 ①②③④⑤⑥⑦
林文琴/2004[9] － 62 月经周期第3天皮下埋植戈舍瑞林3.6 mg，然后1次/28 d，连续3次，末次注射后28 d，Gn促排卵至hCG日 标准黄体期长方案(同上) ②③④⑤⑥
程丹/2010[10] － 90 月经第1～3天皮下注射曲普瑞林3.75 mg(1次/28 d，共2～3支)，末次应用第20～29天后，Gn促排卵至hCG日 前次月经周期第19～21天皮下注射曲普瑞林0.1 mg/d至月经第3天，Gn促排卵至hCG日 ①②③④⑤⑥⑦
表2 纳入7篇文献研究的方法学质量评价
Table 2 Methodology quality evaluation on 7 literatures
纳入文献(第一作者/发表年代) 随机分组方法 分配隐藏 盲法 失访和退出 基线比较 ITT 质量等级
Surrey ES/2002 随机 充分 未提及 无 相似 否 B
Rickes D/2002 随机 充分 未提及 无 相似 否 B
牛海燕/2011 随机 否 未提及 无 相似 否 B
孟晓华/2006 未提及 否 否 无 相似 否 C
邓华丽/2012 未提及 否 否 超长方案组退出7例，长方案组退出26例 相似 是 C
林文琴/2004 随机 否 否 无 相似 否 B
程丹/2010 未提及 否 否 超长方案组退出2例，长方案组退出5例 相似 是 C
图1 超长方案组与长方案组周期取消率的比较
Figure 1 Comparison of cancellation rates between group prolonged protocol and group long protocol
图2 超长方案组与长方案组Gn刺激时间比较
Figure 2 Comparison of gonadotrophins stimulation durations between group prolonged protocol and group long protocol
图3 超长方案组与长方案组Gn总剂量的比较
Figure 3 Comparison of doses of gonadotrophins between group prolonged protocol and group long protocol
图4 超长方案组与长方案获卵数的比较
Figure 4 Comparison of doses of number of oocytes retrieved between group prolonged protocol and group long protocol
图5 超长方案组与长方案hCG日E2值比较
Figure 5 Comparison of erum E2 levels on days of hCG between group prolonged and group long protocol
图6 超长方案组与长方案临床妊娠率的比较
Figure 6 Comparison of clinical pregnancy rates between group prolonged protocol and group long protocol of prolonged protocol and long protocol
图7 超长方案组与长方案流产率的比较
Figure 7 Comparison of abortion rates between group prolonged protocol and group long protocol
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