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浙江大学学报(医学版)  2019, Vol. 48 Issue (2): 165-173    DOI: 10.3785/j.issn.1008-9292.2019.04.07
原著     
子宫内膜异位症合并不孕患者的体外受精促排卵治疗:拮抗剂可代替激动剂吗?
虞雅1(),魏凯1,姚秋萍2,田申1,梁昆3,周黎明3,*(),王丽萍2,*(),金敏1,*()
1. 浙江大学医学院附属第二医院生殖中心, 浙江 杭州 310009
2. 嘉兴市妇幼保健院生殖中心, 浙江 嘉兴 314051
3. 宁波市妇女儿童医院生殖中心, 浙江 宁波 315000
Controlled ovarian stimulation protocols in endometriosis patients: with antagonist or agonist?
YU Ya1(),WEI Kai1,YAO Qiuping2,TIAN Shen1,LIANG Kun3,ZHOU Liming3,*(),WANG Liping2,*(),JIN Min1,*()
1. Reproductive Center, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China
2. Reproductive Center, Jiaxing Women and Children's Hospital, Jiaxing 314051, Zhejiang Province, China
3. Reproductive Center, Ningbo Women and Children's Hospital, Ningbo 315000, Zhejiang Province, China
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摘要:

目的: 对比使用拮抗剂方案、卵泡期长方案和超长方案三种常用促排卵方案的子宫内膜异位症合并不孕患者体外受精-胚胎移植的实验室及临床结局,优化子宫内膜异位症患者,尤其是合并卵巢储备功能下降患者的临床方案选择。方法: 对2017年4月至2018年10月在浙江大学医学院附属第二医院生殖中心、嘉兴市妇幼保健院生殖中心和宁波市妇女儿童医院生殖中心首次进行体外受精治疗的313例子宫内膜异位症合并不孕患者的临床及实验室数据进行回顾性分析,其中采用拮抗剂(拮抗剂组)81例,采用卵泡期长方案(长方案组)148例,采用超长方案(超长方案组)84例。观察不同方案对子宫内膜异位症合并不孕患者体外受精助孕临床和实验室指标的影响。结果: 拮抗剂组患者年龄大于长方案组和超长方案组(均P < 0.05),血清抗苗勒氏管激素值和窦卵泡数少于其他两组(均P < 0.01)。拮抗剂组获卵数、受精数、可利用胚胎数均少于长方案组(均P < 0.05),与超长方案组相近(均P>0.05),三组间受精率、可利用胚胎率差异无统计学意义(P>0.05)。平均每个移植周期,三组间人绒毛膜促性腺激素(HCG)阳性率、临床妊娠率、总胚胎着床率差异均无统计学意义(均P>0.05);拮抗剂组鲜胚着床率低于长方案组(P < 0.05),与超长方案组差异无统计学意义(P>0.05);拮抗剂组冻胚着床率较其他两组有增加的趋势,差异无统计学意义(P>0.05)。卵巢储备功能正常或下降亚组分析结果显示,平均每个移植周期,三组间的HCG阳性率、临床妊娠率、总胚胎着床率差异均无统计学意义(均P>0.05);卵巢储备功能下降患者中,拮抗剂组可利用胚胎率高于长方案组(P < 0.05)。拮抗剂组的促性腺激素总量和用药天数少于长方案组和超长方案组(均P < 0.05)。结论: 子宫内膜异位症合并不孕患者采用拮抗剂方案促排卵,促性腺激素总量少,用药天数短,结合冻胚移植策略,可获得与长方案和超长方案相近的妊娠结局。对于卵巢储备功能下降的子宫内膜异位症患者,拮抗剂方案可获得更高的可利用胚胎率。

关键词: 子宫内膜异位症体外受精胚胎移植妊娠率促性腺素释放激素激动剂/拮抗剂回顾性研究    
Abstract:

Objective: To compare laboratory and clinical outcomes of in vitro fertilization-embryo transfer (IVF-ET) in patients with endometriosis using antagonist protocol, long agonist protocol or prolonged agonist protocol. Methods: Totally 313 patients with endometriosis were recruited in Reproductive Centers of the Second Affiliated Hospital of Zhejiang University School of Medicine, Jiaxing Women and Children's Hospital, and Ningbo Women and Children's Hospital from April 2017 to October 2018, including 81 patients treated with antagonist protocol (antagonist group), 148 treated with long agonist protocol (long agonist group) and 84 treated with prolonged agonist protocol (prolonged agonist group). The clinical and laboratory data of the patients were retrospectively analyzed to investigate the effect of ovarian stimulation protocols on the IVF-ET outcomes of patients with endometriosis. Results: The average age in the antagonist group patients was significantly higher than those in the other two groups (all P < 0.05), and anti-mullerian hormone (AMH) level and antral follicle numbers were significantly lower than those in the other two groups (all P < 0.01). The numbers of average retrieved oocyte, fertilized oocyte and available embryo in the antagonist group were significantly lower than those in the long agonist group (all P < 0.05), but were similar with those in the prolonged agonist group (all P>0.05). Fertilization rate and available embryo rate were comparable among the three groups (all P>0.05). Considering analysis per cycle with embryo transfer, the human chorionic gonadotrophin (HCG) positive rate, clinical pregnancy rate and total implantation rate showed no significant difference among the three groups (all P>0.05). The implantation rate after fresh embryo transfer in the antagonist group was lower than that in the long agonist group (P < 0.05), but was similar with that in the prolonged agonist group (P>0.05). While the implantation rate of freeze-thaw embryo transfer showed a higher trend in the antagonist group, but there was no significant difference (P>0.05). The patients were further divided into diminished and normal ovarian reserve subgroups, the per cycle with embryo transfer, the HCG positive rate, clinical pregnancy rate and total implantation rate still showed no significant difference between two subgroups (all P>0.05), no matter in which ovarian stimulation protocol groups. Besides, in women with diminished ovarian reserve, the available embryo rate in antagonist group was significantly higher than that in the long agonist group (P < 0.05). The amount and duration of Gn application in antagonist group were significantly lower than those in long and prolonged agonist groups (all P < 0.05). Conclusion: Patients with endometriosis who used the antagonist protocol in IVF procedure could reduce the cost and time of Gn treatment, when combined with frozen-embryo transfer strategy the antagonist protocol has comparable clinical pregnancy outcome with long or prolonged agonist protocol, especially in those with diminished ovarian reserve, the higher available embryo rate can be achieved.

Key words: Endometriosis    Fertilization in vitro    Embryo transfer    Pregnancy rate    Gonadotropin-releasing hormone agonists/antagonist    Retrospective studies
收稿日期: 2019-03-22 出版日期: 2019-07-24
CLC:  R711.71  
通讯作者: 周黎明,王丽萍,金敏     E-mail: 3110103563@zju.edu.cn;zhou.li.ming@163.com;wanglipingjxzj@163.com;min_jin@zju.edu.cn
作者简介: 虞雅(1992-), 女, 硕士, 主要从事生殖免疫和生殖内分泌研究; E-mail:3110103563@zju.edu.cn; https://orcid.org/0000-0002-1282-0650
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引用本文:

虞雅,魏凯,姚秋萍,田申,梁昆,周黎明,王丽萍,金敏. 子宫内膜异位症合并不孕患者的体外受精促排卵治疗:拮抗剂可代替激动剂吗?[J]. 浙江大学学报(医学版), 2019, 48(2): 165-173.

YU Ya,WEI Kai,YAO Qiuping,TIAN Shen,LIANG Kun,ZHOU Liming,WANG Liping,JIN Min. Controlled ovarian stimulation protocols in endometriosis patients: with antagonist or agonist?. J Zhejiang Univ (Med Sci), 2019, 48(2): 165-173.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2019.04.07        http://www.zjujournals.com/med/CN/Y2019/V48/I2/165

[$\bar x \pm s$或n(%)]
组别 n 年龄(岁) 体质指数(kg/cm2) 血清AMH值(ng/mL) 窦卵泡数 rAFS Ⅲ/Ⅳ期比例
与长方案组比较,*P<0.05;与超长方案组比较,#P<0.05.AMH:抗苗勒氏管激素;rAFS:美国生殖医学协会修订.
拮抗剂组 81 31.9±3.7*# 20.9±2.6 1.7±1.1*# 6.6±2.9*# 42(51.9)#
长方案组 148 30.7±3.9 21.2±2.6 2.4±1.3 9.3±3.7 61(41.2)#
超长方案组 84 30.2±3.3 20.8±2.4 2.3±1.4 7.9±3.2 67(79.8)
表 1  不同促排卵方案子宫内膜异位症患者一般资料比较
[$\bar x \pm s$或n(%)]
组别 n 年龄(岁) 体质指数(kg/cm2) 血清AMH值(ng/mL) 窦卵泡数 rAFS Ⅲ/Ⅳ期比例
与NOR患者比较,*P<0.05,**P<0.01;与同样卵巢储备功能患者超长方案组比较,#P<0.05;与同样卵巢储备功能患者长方案组比较,P<0.05.DOR:卵巢储备功能下降;NOR:卵巢储备功能正常;AMH:抗苗勒氏管激素;rAFS:美国生殖医学协会修订.
DOR患者 118 31.3±3.9* 20.9±2.7 1.1±0.6** 5.0±1.4** 74(62.7)
  拮抗剂组 46 31.6±3.8 20.6±2.5 0.9±0.5 4.7±1.6 28(60.9)#
  长方案组 39 31.7±4.2 21.2±2.9 1.1±0.4 5.3±1.3 17(43.6)#
  超长方案组 33 30.3±3.4 21.0±2.7 1.1±0.3 5.0±1.3 29(87.9)
NOR患者 195 30.3±3.6 21.1±2.5 2.9±1.1 10.2±2.9 96(49.2)
  拮抗剂组 35 31.2±3.6 21.4±2.9 2.6±0.9# 9.1±2.3 14(40.0)#
  长方案组 109 30.5±4.1 21.2±2.5 2.9±1.2 10.8±3.0 44(40.4)#
  超长方案组 51 30.6±3.2 20.7±2.1 3.1±1.2 9.7±2.6 38(74.5)
表 2  卵巢储备功能下降和卵巢储备功能正常子宫内膜异位症患者一般资料比较
[$\bar x \pm s$或%(n)]
组别 n 获卵数 受精数 可利用胚胎数 受精率 可利用胚胎率 Gn总量(IU) Gn使用天数(d) 每移植周期 胚胎着床率
HCG阳性率 临床妊娠率 总胚胎着床率 冻胚着床率 鲜胚着床率
与长方案组比较,*P<0.05;与超长方案组比较,#P<0.05.Gn:促性腺激素;HCG:人绒毛膜促性腺激素.
拮抗剂组 81 5.7±4.1* 4.4±3.2* 3.2±2.5* 77.4(357/461) 81.9(254/310) 2248±937*# 9.4±2.5*# 56.0(47/84) 50.0(42/84) 32.2(46/143) 40.7(37/91) 17.3(9/52)*
长方案组 148 9.3±4.6 7.2±4.3 4.6±3.1 77.2(1067/1382) 78.5(681/867) 2899±1121 11.0±2.3 50.6(86/170) 46.5(79/170) 34.2(103/301) 31.3(35/112) 36.0(68/189)
超长方案组 84 6.9±3.8* 5.3±3.4* 3.6±2.6* 76.3(441/578) 76.3(299/375) 2991±1003 10.9±2.2 54.6(53/97) 45.4(44/97) 28.0(46/164) 30.0(17/57) 27.1(29/107)
表 3  采用不同促排卵方案的子宫内膜异位症患者体外受精-胚胎移植结局比较
[$\bar x \pm s$或%(n)]
组别 n 获卵数 受精数 可利用胚胎数 受精率 可利用胚胎率 Gn总量(IU) Gn使用天数(d) 每移植周期 胚胎着床率
HCG阳性率 临床妊娠率 总胚胎着床率 冻胚着床率 鲜胚着床率
与长方案组比较,*P<0.05;与超长方案组比较,#P<0.05.Gn:促性腺激素;HCG:人绒毛膜促性腺激素.
拮抗剂组 46 4.0±2.5* 3.1±2.0* 2.4±1.8 78.5(142/181) 80.6(104/129)* 2216±913*# 9.2±2.6*# 52.3(23/44) 45.5(20/44) 29.3(22/75) 35.9(19/53) 13.6(3/22)
长方案组 39 5.6±2.7 4.5±2.0 2.5±1.4 79.1(174/220) 68.3(99/145) 2794±1118 11.3±2.3 41.5(17/41) 39.0(16/41) 28.6(20/70) 25.0(4/16) 29.6(16/54)
超长方案组 33 4.2±2.2* 3.2±2.0* 2.2±1.3 76.1(105/138) 78.5(73/93) 3085±1229 11.5±2.4 51.5(17/33) 42.4(14/33) 29.1(16/55) 25.0(2/8) 29.8(14/47)
表 4  采用不同促排卵方案的卵巢储备功能下降子宫内膜异位症患者体外受精-胚胎移植结局比较
[$\bar x \pm s$或%(n)]
组别 n 获卵数 受精数 可利用胚胎数 受精率 可利用胚胎率 Gn总量(IU) Gn使用天数(d) 每移植周期 胚胎着床率
HCG阳性率 临床妊娠率 总胚胎着床率 冻胚着床率 鲜胚着床率
与长方案组比较,*P<0.05;与超长方案组比较,#P<0.05.Gn:促性腺激素;HCG:人绒毛膜促性腺激素.
拮抗剂组 35 8.0±4.8* 6.1±3.7* 5.2±3.3 76.1(194/255) 83.6(138/165) 2289±980*# 9.7±2.3*# 60.0(24/40) 55.0(22/40) 35.3(24/68) 47.4(18/38) 20.0(6/30)
长方案组 109 10.7±4.4 8.2±4.5 5.3±3.2 76.9(893/1162) 79.1(582/736) 2937±1125 11.2±2.2 53.5(69/129) 48.8(63/129) 35.9(83/231) 32.3(52/135) 38.5(31/96)
超长方案组 51 8.6±3.6* 6.6±3.4* 5.5±3.3 76.4(336/440) 80.1(226/282) 3094±839 11.8±2.3 56.3(36/64) 46.9(30/64) 27.5(30/109) 30.6(15/49) 25.0(15/60)
表 5  采用不同促排卵方案的卵巢储备功能正常子宫内膜异位症患者体外受精-胚胎移植结局比较
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doi: 10.1007/978-1-4419-6066-5
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