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

doi:10.3877/cma.j.issn.1673-5250.2013.03.004

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)
纳入文献(第一作者/发表年代)	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
纳入文献(第一作者/发表年代)	Ⅰ～Ⅱ	Ⅲ～Ⅳ	超长方案组	长方案组	结局指标包括
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)
纳入文献(第一作者/发表年代)	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
纳入文献(第一作者/发表年代)	Ⅰ～Ⅱ	Ⅲ～Ⅳ	超长方案组	长方案组	结局指标包括
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

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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