拮抗剂方案与改良超长方案在卵巢高反应人群中应用的比较
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摘要
目的比较拮抗剂方案与改良超长方案在卵巢高反应患者中应用的临床疗效。方法回顾性分析2015年1月至2017年9月在本院行IVF/ICSI的卵巢高反应患者(获卵数>15个)共853个周期的临床资料。按促排卵方案分为两组,其中拮抗剂方案组186个周期、改良超长方案组667个周期。比较患者的一般情况和临床结局。结果与改良超长方案组比较,拮抗剂方案组Gn总量[(1 544.15±412.52)U vs.(2 949.87±1 156.05)U]、Gn天数[(10.08±1.33)d vs.(13.81±1.87)d]均显著减少(P<0.05),获卵数[(23.41±6.20)vs.(21.96±5.24)]、HCG日E2[(24 087.76±8 309.59)pmol/L vs.(22 281.31±6 830.78)pmol/L]均显著增高(P<0.05),HCG日P/E2值[(0.36±0.20)vs.(0.42±0.20)显著降低(P<0.05);与改良超长方案组比较,拮抗剂方案组胚胎种植率(33.20%vs.46.29%)、临床妊娠率(47.37%vs.63.80%)、抱婴率(32.33%vs.48.86%)均显著降低(P<0.05),但中重度卵巢过度刺激综合征(OHSS)发生率(8.60%vs.15.44%)、移植取消率(28.49%vs.40.78%)亦显著降低(P<0.05)。结论卵巢高反应人群中拮抗剂方案临床结局显著低于改良超长方案,可能与其降低子宫内膜容受性有关,因此应考虑全胚冻存行解冻移植使其降低OHSS风险的同时有良好的妊娠结局。
Objective:To compare the clinical efficacy of GnRH antagonist(GnRH-ant)protocol and modified super-long protocol in the patients with high ovarian response.Methods:The data of 853 IVF/ICSI cycles of the patients with high ovarian response(number of oocytes retrieved >15)in our hospital from Jan.2015 to Sep.2017 were retrospectively analyzed.According to the ovulation induction protocol,they were divided into two groups:the GnRH-ant group(n=186 cycles)and the modified super-long group(n=667 cycles).The general condition and clinical outcome of the patients were compared.Results:Compared to the modified super-long group,the total dosage[(1 544.15±412.52)vs.(2 949.87±1 156.05)U]and days of Gn used[(10.08±1.33)vs.(13.81±1.87)days]were significantly lower(P<0.05).The number of oocytes retrieved[(23.41±6.20)vs.(21.96±5.24)]and the serum E2 levels onHCG day[(24 087.76±8 309.59)vs.(22 281.31±6 830.78)pmol/L]were significantly higher(P<0.05)and the P/E2 value on HCG day[(0.36±0.20)vs.(0.42±0.20)was significantly lower in the antagonist group(P <0.05).The implantation rate(33.20% vs.46.29%),clinical pregnancy rate(47.37% vs.63.80%)and live birth rate(32.33% vs.48.86%)were significantly lower in the antagonist group as compared to the modified super-long group(P<0.05).The incidence of moderate and severe OHSS(8.60% vs.15.44%)and cancellation rate of transplantation(28.49% vs.40.78%)were significantly lower in the antagonist group(P<0.05).Conclusions:The clinical outcome of the antagonist protocol in patients with high ovarian response is significantly lower than that of the modified super-long protocol,which may be related to the reduction of endometrial receptivity,so it should be considered whole embryo cryopreservation for frozen-thawed transplantation to reduce the risk of OHSS to obtain good pregnancy outcome.
Objective:To compare the clinical efficacy of GnRH antagonist(GnRH-ant)protocol and modified super-long protocol in the patients with high ovarian response.Methods:The data of 853 IVF/ICSI cycles of the patients with high ovarian response(number of oocytes retrieved >15)in our hospital from Jan.2015 to Sep.2017 were retrospectively analyzed.According to the ovulation induction protocol,they were divided into two groups:the GnRH-ant group(n=186 cycles)and the modified super-long group(n=667 cycles).The general condition and clinical outcome of the patients were compared.Results:Compared to the modified super-long group,the total dosage[(1 544.15±412.52)vs.(2 949.87±1 156.05)U]and days of Gn used[(10.08±1.33)vs.(13.81±1.87)days]were significantly lower(P<0.05).The number of oocytes retrieved[(23.41±6.20)vs.(21.96±5.24)]and the serum E2 levels onHCG day[(24 087.76±8 309.59)vs.(22 281.31±6 830.78)pmol/L]were significantly higher(P<0.05)and the P/E2 value on HCG day[(0.36±0.20)vs.(0.42±0.20)was significantly lower in the antagonist group(P <0.05).The implantation rate(33.20% vs.46.29%),clinical pregnancy rate(47.37% vs.63.80%)and live birth rate(32.33% vs.48.86%)were significantly lower in the antagonist group as compared to the modified super-long group(P<0.05).The incidence of moderate and severe OHSS(8.60% vs.15.44%)and cancellation rate of transplantation(28.49% vs.40.78%)were significantly lower in the antagonist group(P<0.05).Conclusions:The clinical outcome of the antagonist protocol in patients with high ovarian response is significantly lower than that of the modified super-long protocol,which may be related to the reduction of endometrial receptivity,so it should be considered whole embryo cryopreservation for frozen-thawed transplantation to reduce the risk of OHSS to obtain good pregnancy outcome.
引文
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[10] Alinany HG,Youssef MAFM,Aboulghar M,et al.GnRH antagonists are safer than agonists:an update of a Cochrane review[J].Hum Reprod Update,2011,17:435.
[11] Lainas TG,Sfontouris IA,Zorzovilis IZ,et al.Flexible GnRH antagonist protocol versus GnRH agonist long protocol in patients with polycystic ovary syndrome treated for IVF:a prospective randomised controlled trial(RCT)[J].Hum Reprod,2010,25:683-689.
[12] Gong F,Tang Y,Zhang H,et al.Modified super-long downregulation protocol improved the outcome of in vitro fertilization-embryo transfer in infertile patients[J].J Centl South Univ,2009,34:185-189.
[13] Meng Y,Guo Y,Qian Y,et al.Effects of GnRH antagonist on endometrial protein profiles in the window of implantation[J].Proteomics,2015,14:2350-2359.
[14] Martínez F.Progesterone level and progesterone/estradiol ratio on the day of human chorionic gonadotropin administration:detrimental cutoff levels and new treatment strategy?[J].Fertil Steril,2011,95:1639-1644.
[15] Steward RG,Zhang CE,Shah AA,et al.High Peak Estradiol Predicts Higher Miscarriage and Lower Live Birth Rates in High Responders Triggered with a GnRH Agonist in IVF/ICSI Cycles[J].J Reprod Med,2015,60:463-470.
[16] Eftekhar M,Firouzabadi R D,Karimi H,et al.Outcome of cryopreserved-thawed embryo transfer in the GnRH agonist versus antagonist protocol[J].Iran J Reprod Med,2012,10:297-302.
[2] Mascarenhas M,Balen AH.The high responder:a review of pathophysiology and outcomes during IVF treatment[J].Hum Fertil,2017,20:155-167.
[3]孙赟,朱琴玲.高反应人群应用拮抗剂方案就可避免OHSS发生吗?[J].生殖医学杂志,2015,24:789-792.
[4] Polat M,Bozdag G,Yarali H.Best protocol for controlled ovarian hyperstimulation in assisted reproductive technologies:fact or opinion?[J].Semin Reprod Med,2014,32:262-271.
[5] Lambalk CB,Banga FR,Huirne JA,et al.GnRH antagonist versus long agonist protocols in IVF:a systematic review and meta-analysis accounting for patient type[J].Hum Reprod Update,2017,23:560-579.
[6]龚斐.PCOS患者IVF治疗新策略[D].中南大学,2013.
[7] Gong F,Li X,Zhang S,et al.A modified ultra-long pituitary downregulation protocol improved endometrial receptivity and clinical outcome for infertile patients with polycystic ovarian syndrome[J].Exp Ther Med,2015,10:1865-1870.
[8] Golan A,Weissman A.Symposium:Update on prediction and management of OHSS.A modern classification of OHSS[J/OL].Reprod Biomed Online,2009,19:28-32.
[9] Toftager M,Bogstad J,Bryndorf T,et al.Risk of severe ovarian hyperstimulation syndrome in GnRH antagonist versus GnRH agonist protocol:RCT including 1050 first IVF/ICSI cycles[J].Hum Reprod,2016,31:1253-1264.
[10] Alinany HG,Youssef MAFM,Aboulghar M,et al.GnRH antagonists are safer than agonists:an update of a Cochrane review[J].Hum Reprod Update,2011,17:435.
[11] Lainas TG,Sfontouris IA,Zorzovilis IZ,et al.Flexible GnRH antagonist protocol versus GnRH agonist long protocol in patients with polycystic ovary syndrome treated for IVF:a prospective randomised controlled trial(RCT)[J].Hum Reprod,2010,25:683-689.
[12] Gong F,Tang Y,Zhang H,et al.Modified super-long downregulation protocol improved the outcome of in vitro fertilization-embryo transfer in infertile patients[J].J Centl South Univ,2009,34:185-189.
[13] Meng Y,Guo Y,Qian Y,et al.Effects of GnRH antagonist on endometrial protein profiles in the window of implantation[J].Proteomics,2015,14:2350-2359.
[14] Martínez F.Progesterone level and progesterone/estradiol ratio on the day of human chorionic gonadotropin administration:detrimental cutoff levels and new treatment strategy?[J].Fertil Steril,2011,95:1639-1644.
[15] Steward RG,Zhang CE,Shah AA,et al.High Peak Estradiol Predicts Higher Miscarriage and Lower Live Birth Rates in High Responders Triggered with a GnRH Agonist in IVF/ICSI Cycles[J].J Reprod Med,2015,60:463-470.
[16] Eftekhar M,Firouzabadi R D,Karimi H,et al.Outcome of cryopreserved-thawed embryo transfer in the GnRH agonist versus antagonist protocol[J].Iran J Reprod Med,2012,10:297-302.