黄体期降调节联合人工周期方案在冻融胚胎反复移植失败患者中的应用
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摘要
目的探讨在黄体期用3.75mg GnRH-a降调节预处理对冻融胚胎移植(FET)反复移植失败患者的子宫内膜容受性及临床结局的影响。方法回顾性分析2015年5月至2017年5月在本生殖中心行人工周期方案FET助孕治疗且反复胚胎种植失败(曾移植次数≥2次且均失败,每次移植胚胎数均为2~3枚)的207例患者的临床资料,根据本次内膜准备方案中是否进行GnRH-a降调节预处理分为非降调节组(A组)118例及降调节组(B组)89例。比较两组患者的性激素水平、黄体酮注射日子宫内膜厚度和血流、黄体酮注射日LH水平、临床妊娠率和流产率。并从降调节预处理组中选取46例患者(其前次内膜准备方案均为非降调节的人工周期方案)进行自身对照分析。结果两组患者平均年龄、不孕年限、基础性激素水平、子宫内膜厚度、优胚率、早期流产率比较均无统计学差异(P>0.05),但降调节组子宫内膜A型血流者比例[65.17%(58/89)]、临床妊娠率[55.06%(49/89)]均显著高于非降调节组[分别为38.98%(46/118)、38.98%(46/118)],而降调节组孕酮日LH水平显著低于非降调节组[(10.27±3.79)U/L vs.(1.89±0.78)U/L],差异均有统计学意义(P<0.05);降调节组自身对照分析显示患者的内膜厚度、优胚率均无统计学差异(P>0.05),但降调节预处理后的A型血流者比例[56.52%(26/46)]显著高于前次非降调节周期[32.61%(15/46)](P<0.05)。结论与传统人工周期内膜准备方案比较,黄体期用3.75mg GnRH-a降调节预处理后可显著提高FET周期胚胎反复移植失败患者的子宫内膜容受性和临床妊娠率,而不增加流产率。
Objective:To explore the influences of pre-treatment with 3.75 mg GnRH-a down-regulation in luteal phase on endometrial receptivity and clinical outcomes in patients with repeated implantation failure of frozen-thawed embryo.Methods: The clinical data of 207 patients who accepted FET assisted reproduction technology(ART)with artificial cycle scheme and previously had repeated embryo implantation failures(≥2 times)with 2-3 embryos implantation for each time in our reproductive center from May 2015 to May 2017 were retrospectively analyzed.According to whether or not applying the GnRH-a down-regulation pre-treatment for the endometrium preparation,the patients were divided into down-regulation group(n=118)and non-down-regulation group(n=89).The gonadal hormone levels,endometrium thickness & blood flow and LH level on the day of injecting progesterone,clinical pregnancy rate and abortion rate were compared between the two groups.Forty six patientswho were received non-down-regulation artificial cycle protocols for endometrium preparation in the previously cycles were selected for self-control analysis from the down-regulation pretreatment group.Results:The age,infertility duration,basic sex hormone level,endometrial thickness,high-quality embryo rate and early abortion rate had no statistical difference between the two groups(P>0.05).The proportion of type A blood flow in endometrium [65.17%(58/89)vs.38.98%(46/118)]and clinical pregnancy rate[55.06%(49/89)vs.38.98%(46/118)]in the down-regulation group were significantly higher than non-down-regulation group.LH levels on the day of injecting progesterone in the down-regulation group[(10.27±3.79)vs.(1.89±0.78)U/L]were significantly lower than those the non-down-regulation group(P<0.05).The self-control analysis showed that endometrial thickness and high-quality embryo rate of patients had no significant difference(P>0.05).The proportion of type A blood flow after preconditioning[56.52%(26/46)]was significantly higher than the previous non-down-regulation cycle[32.61%(15/46)](P<0.05).Conclusions:Compared with the traditional artificial cycle scheme for endometrial preparation,pretreatment with 3.75 mg GnRH-a down-regulation can significantly improve endometrial receptivity and clinical pregnancy rate of patients with repeated implantation failure of frozen-thawed embryo,but it does not increase abortion rate.
Objective:To explore the influences of pre-treatment with 3.75 mg GnRH-a down-regulation in luteal phase on endometrial receptivity and clinical outcomes in patients with repeated implantation failure of frozen-thawed embryo.Methods: The clinical data of 207 patients who accepted FET assisted reproduction technology(ART)with artificial cycle scheme and previously had repeated embryo implantation failures(≥2 times)with 2-3 embryos implantation for each time in our reproductive center from May 2015 to May 2017 were retrospectively analyzed.According to whether or not applying the GnRH-a down-regulation pre-treatment for the endometrium preparation,the patients were divided into down-regulation group(n=118)and non-down-regulation group(n=89).The gonadal hormone levels,endometrium thickness & blood flow and LH level on the day of injecting progesterone,clinical pregnancy rate and abortion rate were compared between the two groups.Forty six patientswho were received non-down-regulation artificial cycle protocols for endometrium preparation in the previously cycles were selected for self-control analysis from the down-regulation pretreatment group.Results:The age,infertility duration,basic sex hormone level,endometrial thickness,high-quality embryo rate and early abortion rate had no statistical difference between the two groups(P>0.05).The proportion of type A blood flow in endometrium [65.17%(58/89)vs.38.98%(46/118)]and clinical pregnancy rate[55.06%(49/89)vs.38.98%(46/118)]in the down-regulation group were significantly higher than non-down-regulation group.LH levels on the day of injecting progesterone in the down-regulation group[(10.27±3.79)vs.(1.89±0.78)U/L]were significantly lower than those the non-down-regulation group(P<0.05).The self-control analysis showed that endometrial thickness and high-quality embryo rate of patients had no significant difference(P>0.05).The proportion of type A blood flow after preconditioning[56.52%(26/46)]was significantly higher than the previous non-down-regulation cycle[32.61%(15/46)](P<0.05).Conclusions:Compared with the traditional artificial cycle scheme for endometrial preparation,pretreatment with 3.75 mg GnRH-a down-regulation can significantly improve endometrial receptivity and clinical pregnancy rate of patients with repeated implantation failure of frozen-thawed embryo,but it does not increase abortion rate.
引文
[1]龚雪,蒋霞美.彩色多普勒监测子宫内膜与体外受精-胚胎移植研究进展[J].国际生殖健康/计划生育杂志,2011,30:119-122.
[2]李柳铭,吴洪波,袁华.彩色多普勒超声检测子宫内膜和内膜下血流评价IVF-ET结局[J].生殖与避孕,2008,28:558-562.
[3]Khan KN,Kitajima M,Hiraki K,et al.Cell proliferation effect of GnRH agonist on pathological lesions of women with endometriosis,adenomyosis and uterine myoma[J].Hum Reprod,2010,25:2878-2890.
[4]吴艳霞,杨红玉,常春.子宫内膜异位症不孕患者腹腔镜术后应用GnRH-a对妊娠的影响[J].临床误诊治,2013,26:68-70.
[5]Khan KN,Kitajima M,Hiraki K,et al.Cell proliferation effect of GnRH anonist on pathological lesions of women with endometriosis,adenomy sis and uterine myoma[J].Hum Reprod,2010,25:2878-2890.
[6]Surrey ES,Minjarez DA,Schoolcraft WB.The incidence of aberrant endomentrial alphavbeta(3)vitronectin expression in a high risk infertility population:could prolonged GnRH agonist therapy play a role[J].J Assist Reprod Genet,2007,24:553-556.
[7]黄凤英,刘秋红,王焕萍.GnRH对子宫内膜异位症患者间质细胞分泌VEGF作用的比较[J].中南大学学报(医学版),2010,35:409-418.
[8]吴晓燕,李志凌,林虹,等.多次胚胎移植失败患者采用冻融胚胎移植3种内膜准备方案结局分析[J].中国计划生育学杂志,2014,22:248-251.
[9]陈子江.人类生殖与辅助生殖[M].北京科学出版社,2005:373-375.
[10]Brinsden PR.Textbook of in vitro fertilization and assisted reproduction[M].3rd ed.New York:The Parthenen publishing Group,1999:301.
[11]Ma WG,Song H,Das SK,et al.Estrogen is a crirical determinant that specifies the duration of window of uterine receptivity for implantation[J].Proc Natl Acad Sci U S A,2003,100:2963-2968.
[12]Groenewoud ER,Cantineau AE,Kollen BJ,et al.What is the optimal means of preparing the endometrium in frozen-thawed embryo transfer cycles?A systematic review and metaanalysis[J].Hum Reprod Update,2013,19:458-470.
[13]EI-Toukhy T,Taylor A,Khalaf Y,et al.Pituitary suppression inultrasound-monitored frozen embryo replacement cycles.Arandomised study[J].Hum Reprod,2004,19:874-879.
[14]东亚君,李玉艳,李敏.GnRH-a预处理在冻融胚胎移植中的价值[J].第三军医大学学报,2014,36:1619-1622.
[15]Fatemi HM,Kyrou D,Bourgain C,et al.Cryopreservedthawed human embryo transfer:spontaneous natural cycleis superior to human chorionicgonadotropin-inducednatualcycle[J].Fertil Steril,2010,94:2054-2058.
[16]Al-Inany H,van-Gelder P.Success of frozen embryo transfer:Does the type of gonadotropin influence the outcome?[J].Int J Womens health,2010,2:89-98.
[17]Imai A,Takagi A,Tamaya T.Gonadotropin releasing hormone analog repairs reduced endometrial cell apoptosis in andometriosis in citro[J].Am J Obstet Gynecol,2000,182:42-46.
[18]何茜冬,张婷婷,苏园园,等.Ⅰ~Ⅱ期子宫内膜异位症不孕术后使用促性腺激素释放激素激动剂的随机对照研究[J].生殖医学杂志,2014,23:48-50.
[19]王多静,李霞,腊晓琳.国产醋酸亮丙瑞林在体外受精-胚胎移植超长方案的应用[J].医学生殖杂志,2015,24:115-119.
[20]Tarek A,Gelbaya MD,Luciano G,et al.Cryopreservedthawed embryo transfer in natural or down-regulated hormonally controlled cycles:a retrospective study[J].Fertil Steril,2006,85:603-609.
[21]Sher G,Dodge S,Maassarani G,et al.Management of suboptimal sonographic endometrial patterns in patients undergoing in-Vitrofertilization and eInbryo transfer[J].Hum Reprod,1993,8:347-349.
[22]EI-Toukhy T,Taylor A,Khalaf Y,et al.Pituitary suppression inultrasound-monitored frozen embryo replacement cycles.Arandomised study[J].Hum Reprod,2004,19:874-879.
[23]程婷婷,孙莹璞,苏迎春.降调节联合人工周期方案在冻融胚胎移植周期中的应用[J].生殖与避孕,2013,33:167-172.
[24]郭慧,龚斐,罗克丽.两种雌孕激素替代法内膜准备对多囊卵巢综合征冷冻胚胎移植临床效果的比较[J].中国现代医学杂志,2013,19:74-77.
[2]李柳铭,吴洪波,袁华.彩色多普勒超声检测子宫内膜和内膜下血流评价IVF-ET结局[J].生殖与避孕,2008,28:558-562.
[3]Khan KN,Kitajima M,Hiraki K,et al.Cell proliferation effect of GnRH agonist on pathological lesions of women with endometriosis,adenomyosis and uterine myoma[J].Hum Reprod,2010,25:2878-2890.
[4]吴艳霞,杨红玉,常春.子宫内膜异位症不孕患者腹腔镜术后应用GnRH-a对妊娠的影响[J].临床误诊治,2013,26:68-70.
[5]Khan KN,Kitajima M,Hiraki K,et al.Cell proliferation effect of GnRH anonist on pathological lesions of women with endometriosis,adenomy sis and uterine myoma[J].Hum Reprod,2010,25:2878-2890.
[6]Surrey ES,Minjarez DA,Schoolcraft WB.The incidence of aberrant endomentrial alphavbeta(3)vitronectin expression in a high risk infertility population:could prolonged GnRH agonist therapy play a role[J].J Assist Reprod Genet,2007,24:553-556.
[7]黄凤英,刘秋红,王焕萍.GnRH对子宫内膜异位症患者间质细胞分泌VEGF作用的比较[J].中南大学学报(医学版),2010,35:409-418.
[8]吴晓燕,李志凌,林虹,等.多次胚胎移植失败患者采用冻融胚胎移植3种内膜准备方案结局分析[J].中国计划生育学杂志,2014,22:248-251.
[9]陈子江.人类生殖与辅助生殖[M].北京科学出版社,2005:373-375.
[10]Brinsden PR.Textbook of in vitro fertilization and assisted reproduction[M].3rd ed.New York:The Parthenen publishing Group,1999:301.
[11]Ma WG,Song H,Das SK,et al.Estrogen is a crirical determinant that specifies the duration of window of uterine receptivity for implantation[J].Proc Natl Acad Sci U S A,2003,100:2963-2968.
[12]Groenewoud ER,Cantineau AE,Kollen BJ,et al.What is the optimal means of preparing the endometrium in frozen-thawed embryo transfer cycles?A systematic review and metaanalysis[J].Hum Reprod Update,2013,19:458-470.
[13]EI-Toukhy T,Taylor A,Khalaf Y,et al.Pituitary suppression inultrasound-monitored frozen embryo replacement cycles.Arandomised study[J].Hum Reprod,2004,19:874-879.
[14]东亚君,李玉艳,李敏.GnRH-a预处理在冻融胚胎移植中的价值[J].第三军医大学学报,2014,36:1619-1622.
[15]Fatemi HM,Kyrou D,Bourgain C,et al.Cryopreservedthawed human embryo transfer:spontaneous natural cycleis superior to human chorionicgonadotropin-inducednatualcycle[J].Fertil Steril,2010,94:2054-2058.
[16]Al-Inany H,van-Gelder P.Success of frozen embryo transfer:Does the type of gonadotropin influence the outcome?[J].Int J Womens health,2010,2:89-98.
[17]Imai A,Takagi A,Tamaya T.Gonadotropin releasing hormone analog repairs reduced endometrial cell apoptosis in andometriosis in citro[J].Am J Obstet Gynecol,2000,182:42-46.
[18]何茜冬,张婷婷,苏园园,等.Ⅰ~Ⅱ期子宫内膜异位症不孕术后使用促性腺激素释放激素激动剂的随机对照研究[J].生殖医学杂志,2014,23:48-50.
[19]王多静,李霞,腊晓琳.国产醋酸亮丙瑞林在体外受精-胚胎移植超长方案的应用[J].医学生殖杂志,2015,24:115-119.
[20]Tarek A,Gelbaya MD,Luciano G,et al.Cryopreservedthawed embryo transfer in natural or down-regulated hormonally controlled cycles:a retrospective study[J].Fertil Steril,2006,85:603-609.
[21]Sher G,Dodge S,Maassarani G,et al.Management of suboptimal sonographic endometrial patterns in patients undergoing in-Vitrofertilization and eInbryo transfer[J].Hum Reprod,1993,8:347-349.
[22]EI-Toukhy T,Taylor A,Khalaf Y,et al.Pituitary suppression inultrasound-monitored frozen embryo replacement cycles.Arandomised study[J].Hum Reprod,2004,19:874-879.
[23]程婷婷,孙莹璞,苏迎春.降调节联合人工周期方案在冻融胚胎移植周期中的应用[J].生殖与避孕,2013,33:167-172.
[24]郭慧,龚斐,罗克丽.两种雌孕激素替代法内膜准备对多囊卵巢综合征冷冻胚胎移植临床效果的比较[J].中国现代医学杂志,2013,19:74-77.