微刺激促排卵在卵巢低反应不孕患者中的应用
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摘要
目的探讨微刺激促排卵方案在卵巢低反应(POR)患者IVF/ICSI-ET中的临床应用价值。方法回顾性分析2016年1月至2017年12月在我院生殖中心行IVF/ICSI-ET治疗,1年内分别行微刺激方案与其他常规方案促排卵的102例患者。并根据患者不同情况分为两组:预期POR组(70例),未预期POR组(32例)。对每例患者前后不同促排方案治疗周期的临床数据及结果进行分析。结果预期POR组中,微刺激周期与其他常规促排卵周期比较,HCG日E2水平、获卵数、MⅡ卵数、2PN数、优胚数、可利用胚胎数以及优胚率、可利用胚胎率的组间差异均无统计学意义(P>0.05);Gn天数[(8.59±2.52)vs.(10.72±2.57)d]、Gn总量[(2 007.42±930.22)vs.(3 276.56±1 309.50)U]显著降低,且MⅡ卵率(72.15%vs.57.33%)、正常受精率(68.95%vs.59.48%)显著升高,差异均有统计学意义(P<0.05)。未预期POR组中,微刺激周期与其他常规促排卵周期比较,Gn天数[(9.03±1.26)vs.(11.72±2.44)d]、Gn总量[(1 863.28±314.24)vs.(3 160.55±1 216.86)U]显著降低,差异均有统计学意义(P<0.05);HCG日E2水平、获卵数、MⅡ卵数、2PN数、优胚数、可利用胚胎数以及MⅡ卵率、正常受精率、优胚率、可利用胚胎率比较,差异均无统计学意义(P>0.05)。结论对于预期的POR患者,微刺激方案可以获得较高的MⅡ卵率和正常受精率;而对于未预期的POR患者,微刺激方案可以减少Gn的用量和天数,但并不能改善其助孕结局。
Objective:To explore the clinical application value of mild stimulation ovulation induction for patients with poor ovarian response(POR)in IVF/ICSI-ET.Methods:The data of 102 patients undergone IVF/ICSI-ET in Department ART of our hospital from January 2016 to December 2017 were retrospectively analyzed.The patients were respectively treated with mild ovarian stimulation protocol and conventional stimulation protocol in one year.The patients were divided into two groups:expected POR group(n=70),unexpected POR group(n=32).The clinical data and results of the two groups were compared.Results:In the expected POR group,there were no significant differences in E21 evels on the HCG day,number of oocytes retrieved,MⅡ oocytes,normal fertilized oocytes,good quality embryos,available embryos and good quality embryo rate,available embryo rate between mild ovarian stimulation cycles and convention stimulation cycles(P>0.05).The duration[(8.59±2.52)vs.(10.72±2.57)days)]and the total dosage[(2 007.42±930.22)vs.(3 276.56±1 309.50)U]of gonadotropin(Gn)used in mild ovarian stimulation cycles were significantly less than those in convention stimulation cycles(P<0.05).The MⅡoocyte rate(72.15% vs.57.33%)and normal fertilization rate(68.95% vs.59.48%)in mild ovarian stimulation cycles were significantly higher than those in convention stimulation cycles(P<0.05).In the unexpected POR group,there were no significant differences in E21 evels on the HCG day,number of oocytes retrieved,MⅡoocytes,normal fertilized oocytes,good quality embryos,available embryos and MⅡoocyte rate,normal fertilization rate,good quality embryo rate,available embryo rate between mild ovarian stimulation cycles and convention stimulation cycles(P>0.05).The duration[(9.03±1.26)vs.(11.72±2.44)days]and the total dosage[(1 863.28±314.24)vs.(3 160.55±1 216.86)U]of Gn used in mild ovarian stimulation cycles were significantly less than those in convention stimulation cycles(P<0.05).Conclusions:Mild ovarian stimulation protocol can obtain higher MⅡ rate and normal fertilization rate in the patients with expected POR.For the patients with unexpected POR,mild stimulation ovulation can reduce the duration and the total dosage of Gn used,while cannot improve the outcome of IVF/ICSI-ET.
Objective:To explore the clinical application value of mild stimulation ovulation induction for patients with poor ovarian response(POR)in IVF/ICSI-ET.Methods:The data of 102 patients undergone IVF/ICSI-ET in Department ART of our hospital from January 2016 to December 2017 were retrospectively analyzed.The patients were respectively treated with mild ovarian stimulation protocol and conventional stimulation protocol in one year.The patients were divided into two groups:expected POR group(n=70),unexpected POR group(n=32).The clinical data and results of the two groups were compared.Results:In the expected POR group,there were no significant differences in E21 evels on the HCG day,number of oocytes retrieved,MⅡ oocytes,normal fertilized oocytes,good quality embryos,available embryos and good quality embryo rate,available embryo rate between mild ovarian stimulation cycles and convention stimulation cycles(P>0.05).The duration[(8.59±2.52)vs.(10.72±2.57)days)]and the total dosage[(2 007.42±930.22)vs.(3 276.56±1 309.50)U]of gonadotropin(Gn)used in mild ovarian stimulation cycles were significantly less than those in convention stimulation cycles(P<0.05).The MⅡoocyte rate(72.15% vs.57.33%)and normal fertilization rate(68.95% vs.59.48%)in mild ovarian stimulation cycles were significantly higher than those in convention stimulation cycles(P<0.05).In the unexpected POR group,there were no significant differences in E21 evels on the HCG day,number of oocytes retrieved,MⅡoocytes,normal fertilized oocytes,good quality embryos,available embryos and MⅡoocyte rate,normal fertilization rate,good quality embryo rate,available embryo rate between mild ovarian stimulation cycles and convention stimulation cycles(P>0.05).The duration[(9.03±1.26)vs.(11.72±2.44)days]and the total dosage[(1 863.28±314.24)vs.(3 160.55±1 216.86)U]of Gn used in mild ovarian stimulation cycles were significantly less than those in convention stimulation cycles(P<0.05).Conclusions:Mild ovarian stimulation protocol can obtain higher MⅡ rate and normal fertilization rate in the patients with expected POR.For the patients with unexpected POR,mild stimulation ovulation can reduce the duration and the total dosage of Gn used,while cannot improve the outcome of IVF/ICSI-ET.
引文
[1]高彦,冒韵东,王媁,等.卵巢功能减退患者采用自然周期或微刺激方案治疗策略及结局[J].生殖医学杂志,2016,25:897-900.
[2]乔宗惠,吴丽敏,庞丽娥,等.卵巢储备功能下降患者应用双刺激方案、微刺激方案、黄体期促排方案的妊娠结局比较[J].生殖医学杂志,2017,26:433-437.
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[7]曹蓓,李艳萍,刘冬娥,等.微刺激方案与常规促排卵方案在高龄卵巢低反应不育女性中的前后周期比较[J].生殖医学杂志,2014,23:709-713.
[8]田莉,柏海燕,李昭荣,等.卵巢低反应患者应用超短方案及微刺激方案促排卵的效果比较[J].生殖医学杂志,2013,22:762-766.
[9]Lazer T,Dar S,Shlush E,et al.Comparison of IVF Outcomes between Minimal Stimulation and High-Dose Stimulation for Patients with Poor Ovarian Reserve[J].Int J Reprod Med,2014,2014:581451.
[10]Ragni G,Levi-Setti PE,Fadini R,et al.Clomiphene citrate versus high doses of gonadotropins for in vitro fertilisation in women with compromised ovarian reserve:a randomised controlled noninferiority trial[J].Reprod Biol Endocrinol,2012,10:114.
[11]Casano S,Guidetti D,Patriarca A,et al.MILD ovarian stimulation with GnRH-antagonist vs.long protocol with low dose FSH for non-PCO high responders undergoing IVF:a prospective,randomized study including thawing cycles[J].JAssist Reprod Genet,2012,29:1343-1351.
[12]Baker VL,Brown MB,Luke B,et al.Gonadotropin dose is negatively correlated with live birth rate:analysis of more than 650,000assisted reproductive technology cycles[J].Fertil Steril,2015,104:1145-1152.e1-5.
[13]Ferraretti AP,Gianaroli L,Magli MC,et al.Mild ovarian stimulation with clomiphene citrate launch is a realistic option for in vitro fertilization[J].Fertil Steril,2015,104:333-338.
[14]Zhang JJ,Merhi Z,Yang M,et al.Minimal stimulation IVFvs conventional IVF:a randomized controlled trial[J].Am JObstet Gynecol,2016,214:96.e1-8.
[15]Matsaseng T,Kruger T,Steyn W.Mild ovarian stimulation for in vitro fertilization:are we ready to change?A metaanalysis[J].Gynecol Obstet Invest,2013,76:233-240.
[16]Karimzadeh MA,Ahmadi S,Oskouian H,et al.Comparison of mild stimulation and conventional stimulation in ARToutcome[J].Arch Gynecol Obstet,2010,281:741-746.
[17]匡延平.微刺激促排卵方案的临床研究[J].生殖医学杂志,2010,19:356-359.
[18]Youssef MA,van Wely M,Al-Inany H,et al.A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF:a multicenter randomized non-inferiority trial[J].Hum Reprod,2017,32:112-118.
[19]Mohsen IA,El Din RE.Minimal stimulation protocol using letrozole versus microdose flare up GnRH agonist protocol in women with poor ovarian response undergoing ICSI[J].Gynecol Endocrinol,2013,29:105-108.
[2]乔宗惠,吴丽敏,庞丽娥,等.卵巢储备功能下降患者应用双刺激方案、微刺激方案、黄体期促排方案的妊娠结局比较[J].生殖医学杂志,2017,26:433-437.
[3]Gianaroli L,Magli MC,Cavallini G,et al.Predicting aneuploidy in human oocytes:key factors which affect the meiotic process[J].Hum Reprod,2010,25:2374-2386.
[4]Verberg MF,Eijkemans MJ,Macklon NS,et al.The clinical significance of the retrieval of a low number of oocytes following mild ovarian stimulation for IVF:a meta-analysis[J].Hum Reprod Update,2009,15:5-12.
[5]Baart EB,Martini E,Eijkemans MJ,et al.Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo:a randomized controlled trial[J].Hum Reprod,2007,22:980-988.
[6]Song D,Shi Y,Zhong Y,et al.Efficiency of mild ovarian stimulation with clomiphene on poor ovarian responders during IVF\ICSI procedures:a meta-analysis[J].Eur JObstet Gynecol Reprod Biol,2016,204:36-43.
[7]曹蓓,李艳萍,刘冬娥,等.微刺激方案与常规促排卵方案在高龄卵巢低反应不育女性中的前后周期比较[J].生殖医学杂志,2014,23:709-713.
[8]田莉,柏海燕,李昭荣,等.卵巢低反应患者应用超短方案及微刺激方案促排卵的效果比较[J].生殖医学杂志,2013,22:762-766.
[9]Lazer T,Dar S,Shlush E,et al.Comparison of IVF Outcomes between Minimal Stimulation and High-Dose Stimulation for Patients with Poor Ovarian Reserve[J].Int J Reprod Med,2014,2014:581451.
[10]Ragni G,Levi-Setti PE,Fadini R,et al.Clomiphene citrate versus high doses of gonadotropins for in vitro fertilisation in women with compromised ovarian reserve:a randomised controlled noninferiority trial[J].Reprod Biol Endocrinol,2012,10:114.
[11]Casano S,Guidetti D,Patriarca A,et al.MILD ovarian stimulation with GnRH-antagonist vs.long protocol with low dose FSH for non-PCO high responders undergoing IVF:a prospective,randomized study including thawing cycles[J].JAssist Reprod Genet,2012,29:1343-1351.
[12]Baker VL,Brown MB,Luke B,et al.Gonadotropin dose is negatively correlated with live birth rate:analysis of more than 650,000assisted reproductive technology cycles[J].Fertil Steril,2015,104:1145-1152.e1-5.
[13]Ferraretti AP,Gianaroli L,Magli MC,et al.Mild ovarian stimulation with clomiphene citrate launch is a realistic option for in vitro fertilization[J].Fertil Steril,2015,104:333-338.
[14]Zhang JJ,Merhi Z,Yang M,et al.Minimal stimulation IVFvs conventional IVF:a randomized controlled trial[J].Am JObstet Gynecol,2016,214:96.e1-8.
[15]Matsaseng T,Kruger T,Steyn W.Mild ovarian stimulation for in vitro fertilization:are we ready to change?A metaanalysis[J].Gynecol Obstet Invest,2013,76:233-240.
[16]Karimzadeh MA,Ahmadi S,Oskouian H,et al.Comparison of mild stimulation and conventional stimulation in ARToutcome[J].Arch Gynecol Obstet,2010,281:741-746.
[17]匡延平.微刺激促排卵方案的临床研究[J].生殖医学杂志,2010,19:356-359.
[18]Youssef MA,van Wely M,Al-Inany H,et al.A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF:a multicenter randomized non-inferiority trial[J].Hum Reprod,2017,32:112-118.
[19]Mohsen IA,El Din RE.Minimal stimulation protocol using letrozole versus microdose flare up GnRH agonist protocol in women with poor ovarian response undergoing ICSI[J].Gynecol Endocrinol,2013,29:105-108.