卵巢刺激慢反应患者补充生长激素的疗效评价
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摘要
目的探讨在体外受精-胚胎移植(in vitro fertilization-embryo transfer,IVF-ET)中对卵巢刺激慢反应患者补充生长激素(growth hormone,GH)的疗效。方法选取2014年6月至2017年12月在石家庄市第四医院生殖中心接受IVF-ET治疗的患者130例,采用常规长方案,促性腺激素(gonadotropins,Gn)使用后第6～8 d阴道B超监测卵泡发育情况,并检测血清黄体生成素(luteinizing hormone,LH)、卵泡刺激素(follicle-stimulating hormone,FSH)、雌二醇(estradiol,E_2)、孕酮(progesterone,P)水平。所有患者均符合卵巢慢反应(suboptimal ovarian response,SOR)标准,根据患者用药不同分为两组,研究组(72例)在添加尿促性素(human menopausal gonadotropin, HMG)同时加用GH 4.5 IU/d至绒毛膜促性腺激素(human choionic gonadotophin,hCG)日;对照组(68例)只添加HMG。分析两组临床资料和妊娠结局。结果两组患者年龄、体质量指数、Gn启动日LH、FSH及E_2水平、窦卵泡数目、hCG日子宫内膜厚度方面比较,差异均无统计学意义(P>0.05)。研究组Gn使用天数、Gn使用量及HMG使用量低于对照组,获卵数目及受精数高于对照组,差异均有统计学意义(P<0.05);研究组卵裂数、hCG日E_2水平、优胚数及妊娠率均高于对照组,但差异无统计学意义(P>0.05)。结论 SOR患者添加GH可减少Gn用量、Gn使用天数及HMG用量,增加获卵数及受精数。
Objective To investigate the effect of supplementation of growth hormone(GH) on patients with suboptimal ovarian response(SOR)in in vitro fertilization and embryo transfer(IVF-ET). Methods From June 2014 to December 2017, 130 patients were treated with IVF-ET in the reproductive center of the Fourth Hospital of Shijiazhuang City, all patients were treated with conventional long prescription, and the development of follicular was monitored by vaginal ultrasound after gonadotropins(Gn) administration 6～8 days, and the levels of luteinizing hormone(LH), follicle-stimulating hormone(FSH), estradiol(E_2), progesterone(P) were tested. All patients met the criteria of SOR. They were divided into two groups according to different medications. The study group(72 cases) was treated with human menopausal gonadotropin(HMG) and GH 4.5 IU/d to the day of human chorionic gonadotropin(hCG) administration, while the control group(68 cases) was only treated with HMG. The clinical data and pregnancy outcomes of the two groups were analyzed. Results There were no significant differences in age, body mass index, LH, FSH and E_2 levels on Gn initiation day, number of sinus follicles and endometrial thickness in the day of hCG administration between the two groups(P>0.05). The days of Gn, the total dosages of Gn and HMG in the study group were lower than those in the control group, and the number of eggs obtained and fertilized were higher than those in the control group(P<0.05); the cleavage number, E_2 level in the day of hCG administration, number of good embryos and pregnancy rate in the study group were higher than those in the control group, but there were no significant statiscal difference(P>0.05). Conclusion Adding GH to SOR patients can reduce the dosage of Gn and HMG, the days of Gn used and increase the number of eggs and fertilization.
Objective To investigate the effect of supplementation of growth hormone(GH) on patients with suboptimal ovarian response(SOR)in in vitro fertilization and embryo transfer(IVF-ET). Methods From June 2014 to December 2017, 130 patients were treated with IVF-ET in the reproductive center of the Fourth Hospital of Shijiazhuang City, all patients were treated with conventional long prescription, and the development of follicular was monitored by vaginal ultrasound after gonadotropins(Gn) administration 6～8 days, and the levels of luteinizing hormone(LH), follicle-stimulating hormone(FSH), estradiol(E_2), progesterone(P) were tested. All patients met the criteria of SOR. They were divided into two groups according to different medications. The study group(72 cases) was treated with human menopausal gonadotropin(HMG) and GH 4.5 IU/d to the day of human chorionic gonadotropin(hCG) administration, while the control group(68 cases) was only treated with HMG. The clinical data and pregnancy outcomes of the two groups were analyzed. Results There were no significant differences in age, body mass index, LH, FSH and E_2 levels on Gn initiation day, number of sinus follicles and endometrial thickness in the day of hCG administration between the two groups(P>0.05). The days of Gn, the total dosages of Gn and HMG in the study group were lower than those in the control group, and the number of eggs obtained and fertilized were higher than those in the control group(P<0.05); the cleavage number, E_2 level in the day of hCG administration, number of good embryos and pregnancy rate in the study group were higher than those in the control group, but there were no significant statiscal difference(P>0.05). Conclusion Adding GH to SOR patients can reduce the dosage of Gn and HMG, the days of Gn used and increase the number of eggs and fertilization.
引文
[1] 乔杰,马彩虹,刘嘉茵,等.辅助生殖促排卵药物治疗专家共识[J].生殖与避孕,2015,35,(4):211-223.
[2] Yaz1c1 YF,G?rkemli H,?olakogg MC,et al.The evaluation of recombinant LH supplementation in patients with suboptimal response to recombinant FSH undergoing IVF treatment with GnRH agonist down-regulation[J].Gynecol Endocrinol,2015,31(2):141-144.
[3] 张鑫,罗清炳,徐鸿毅,等.控制性超促排卵后卵巢慢反应与体外受精结局的关系的研究 [J].中国性科学,2016,25(6):114-117.
[4] Papaleo E,Vanni VS,Vigano P,et al.Recombinant LH administration in subsequent cycle after "unexpected" poor response to recombinant FSH monotherapy [J].Gynecol Endocrinol,2014,30 (11) :813-816.
[5] Alviggi C,Pettersson K,Longobardi S,et al.A common polymorphicallele of the LH beta-subunit gene is associated with higher exogenous FSH consumption during controlled ovarian stimulation for assisted reproductive technology[J].Reprod Biol Endocrinol,2013(11):51.
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[7] Yin QQ,Zheng JH,Hang J,et al.Rs13405728 is associated with slow ovarian response in assisted reproductive technology [J].Eur Rev Med Pharmacol Sci,2018,22(15):4757-4761.
[8] 汤文娟,刘雨生,黄玲莉.PCOS患者促排卵过程中发生卵巢慢反应的影响因素分析[J].生殖医学杂志,2016,25(5):395-400.
[9] 赵梓彤,刘冬娥.多囊卵巢综合征GnRH-a长方案卵巢慢反应相关因素分析 [J].中国实用妇科与产科杂志,2016,32(10):1006-1011.
[10] 高明霞,马晓玲,张学红,等.卵巢慢反应患者控制性超促排卵相关因素分析:一项多中心回顾性研究 [J].中华生殖与避孕杂志,2017,37(9):698-702.
[11] Yazcylamz F,Grkemli H,Olakolu MC,et al.The evulation of recombination LH supplementation in patients with suboptimak response to recombinant FSH undergoing IVF treatment with GnRH agonist down-regulation [J].Gynecol Endocrinol,2015,31(2):141-144.
[12] 陈丽文,冯若凡.黄体生成素对控制性超促排卵过程中卵巢慢反应患者临床结局的影响 [J].现代中西医结合杂志,2016,25(11) :1189-1192.
[13] 王海燕.u-FSH联合HMG对控制性超排卵中长效GnRH-a降调节后妊娠结局的影响 [J].现代诊断与治疗,2017,28(12):2218-2219.
[14] 唐静,赵梓彤,李玉梅,等.不同时期添加黄体生成素对多囊卵巢综合征GnRH-a长方案卵巢慢反应患者临床结局的影响 [J].湖南师范大学学报,2018,15(4):56-60.
[15] Luque RM,Kineman RD.Impact of obesity on the growth hormone axis:evidence for a direct inhibitory effect of hyperinsulinemia on pituitary function[J].Endocrinology,2006,147(6):2754-2763.
[16] Reed BG,Babayev SN,Bukulmez O.Shifting paradigms in diminished ovarian reserve and advanced reproductive age in assisted reproduction:customization instead of conformity [J].Semin Reprod Med,2015,33(3):169-178.
[17] Slot KA,Kastelijn J,Bachelot A,et al.Reduced recruitment and survival of primordial and growing follicles in GH receptor-deficient mice [J].Reproduction,2006,131(3):525-532.
[18] Yu X,Ruan J,He LP,et al.Efficacy of growth hormone supplementation with gonadotrophins in vitro fertilization for poor ovarian responders:an updated meta-analysis [J].Int J Clin Exp Med,2015,8(4):4954-4967.
[19] Serafim MK,Duarte AB,Silva GM,et al.Impact of grow hormone(GH) ang follicle stimulating hormone(FSH) on invitro canine preantral follicle development and estradiol production [J].Growth Horm IGF Res,2015,25:85-89.
[2] Yaz1c1 YF,G?rkemli H,?olakogg MC,et al.The evaluation of recombinant LH supplementation in patients with suboptimal response to recombinant FSH undergoing IVF treatment with GnRH agonist down-regulation[J].Gynecol Endocrinol,2015,31(2):141-144.
[3] 张鑫,罗清炳,徐鸿毅,等.控制性超促排卵后卵巢慢反应与体外受精结局的关系的研究 [J].中国性科学,2016,25(6):114-117.
[4] Papaleo E,Vanni VS,Vigano P,et al.Recombinant LH administration in subsequent cycle after "unexpected" poor response to recombinant FSH monotherapy [J].Gynecol Endocrinol,2014,30 (11) :813-816.
[5] Alviggi C,Pettersson K,Longobardi S,et al.A common polymorphicallele of the LH beta-subunit gene is associated with higher exogenous FSH consumption during controlled ovarian stimulation for assisted reproductive technology[J].Reprod Biol Endocrinol,2013(11):51.
[6] Yao Y,Ma CH,Tang HL,et al.Influence of follicle-stimulating hormone receptor (FSHR) Ser680Asn polymorphism on ovarian function and in-vitro fertilization outcome:A meta-analysis [J].Mol GenetMetab,2011,103(4):388-393.
[7] Yin QQ,Zheng JH,Hang J,et al.Rs13405728 is associated with slow ovarian response in assisted reproductive technology [J].Eur Rev Med Pharmacol Sci,2018,22(15):4757-4761.
[8] 汤文娟,刘雨生,黄玲莉.PCOS患者促排卵过程中发生卵巢慢反应的影响因素分析[J].生殖医学杂志,2016,25(5):395-400.
[9] 赵梓彤,刘冬娥.多囊卵巢综合征GnRH-a长方案卵巢慢反应相关因素分析 [J].中国实用妇科与产科杂志,2016,32(10):1006-1011.
[10] 高明霞,马晓玲,张学红,等.卵巢慢反应患者控制性超促排卵相关因素分析:一项多中心回顾性研究 [J].中华生殖与避孕杂志,2017,37(9):698-702.
[11] Yazcylamz F,Grkemli H,Olakolu MC,et al.The evulation of recombination LH supplementation in patients with suboptimak response to recombinant FSH undergoing IVF treatment with GnRH agonist down-regulation [J].Gynecol Endocrinol,2015,31(2):141-144.
[12] 陈丽文,冯若凡.黄体生成素对控制性超促排卵过程中卵巢慢反应患者临床结局的影响 [J].现代中西医结合杂志,2016,25(11) :1189-1192.
[13] 王海燕.u-FSH联合HMG对控制性超排卵中长效GnRH-a降调节后妊娠结局的影响 [J].现代诊断与治疗,2017,28(12):2218-2219.
[14] 唐静,赵梓彤,李玉梅,等.不同时期添加黄体生成素对多囊卵巢综合征GnRH-a长方案卵巢慢反应患者临床结局的影响 [J].湖南师范大学学报,2018,15(4):56-60.
[15] Luque RM,Kineman RD.Impact of obesity on the growth hormone axis:evidence for a direct inhibitory effect of hyperinsulinemia on pituitary function[J].Endocrinology,2006,147(6):2754-2763.
[16] Reed BG,Babayev SN,Bukulmez O.Shifting paradigms in diminished ovarian reserve and advanced reproductive age in assisted reproduction:customization instead of conformity [J].Semin Reprod Med,2015,33(3):169-178.
[17] Slot KA,Kastelijn J,Bachelot A,et al.Reduced recruitment and survival of primordial and growing follicles in GH receptor-deficient mice [J].Reproduction,2006,131(3):525-532.
[18] Yu X,Ruan J,He LP,et al.Efficacy of growth hormone supplementation with gonadotrophins in vitro fertilization for poor ovarian responders:an updated meta-analysis [J].Int J Clin Exp Med,2015,8(4):4954-4967.
[19] Serafim MK,Duarte AB,Silva GM,et al.Impact of grow hormone(GH) ang follicle stimulating hormone(FSH) on invitro canine preantral follicle development and estradiol production [J].Growth Horm IGF Res,2015,25:85-89.