卵巢反应不良患者第二周期促排卵个体化治疗结局

目的探讨第1周期促排卵卵巢反应不良患者第2周期采用个体化方案治疗的结局。方法 2008年1月至2010年12月在山东大学附属省立医院生殖医学中心行体外受精-胚胎移植或卵母细胞浆内单精子注射（IVF/ICSI-ET）第1周期常规方案促排卵发生卵巢反应不良患者239例,第2周期采用个体化促排卵方案,将其分为两组：第1周期、第2周期获卵数均〈5个者104例为A组;第1周期获卵数〈5个,但第2周期获卵数≥5个者135例为B组;比较两组的治疗情况和临床结局。结果①A组和B组第2周期长方案的应用较第1周期减少,而短方案、微刺激方案、其他方案应用比例增加（P〈0.05）;②A组第2周期生长激素应用率（56.7%）高于第1周期（26.0%;P〈0.05）;B组第2周期生长激素应用率（45.9%）均高于第1周期（17.0%;P〈0.01）;③A组第2周期Gn启动量[（244±101）U]高于第1周期[（218±56）U;P〈0.05];B组第2周期Gn启动量[（229±68）U]高于第1周期[（204±61）U;P〈0.01],但两组Gn总量及Gn刺激时间比较,差异均无统计学意义（P〉0.05）。④A组两个周期hCG日血E2峰值、〉14mm卵泡数、获卵数、优质胚胎数及胚胎移植取消率比较,差异均无统计学意义（P〉0.05）,但第2周期移植胚胎数目[（2.0±0.8）个]及临床妊娠率（30.9%）均较第1周期[（1.6±0.7）个;4.7%]显著增加（P〈0.01）。B组第2周期的hCG日血E2峰值、〉14mm卵泡数、获卵数、优质胚胎数、移植胚胎数及临床妊娠率分别为（10789.8±6246.3）pmol/L、（7.1±3.9）个、（8.1±3.5）个、（3.3±2.1）个、（2.6±0.6）个和40.3%,第1周期分别为（6595.0±4470.1）pmol/L、（4.3±2.5）个、（3.0±1.1）个、（1.5±1.1）个、（2.0±0.7）个和11.6%,两周期各指标比较,差异均有统计学意义（P〈0.01）。B组第2周期无胚胎移植取消周期率（8.1%）低于第1周期（25.9%;P〈0.01）。结论第1周期常规方案促排卵卵巢反应不良患者,在第2周期加大Gn启动量、增加短方案或微刺激方案、加用生长激素等个体化治疗,43.5%的患者仍发生卵巢反应不良,但所有患者的治疗结局均显著改善。

Outcomes of the individualized treatment in poor responders undergoing the 2nd IVF treatment cycles

Objective To investigate the effect of individualized treatment on the outcomes of the second IVF treatment cycles for the patients with history of poor ovarian response.Methods 239women who received their second IVF/ICSI-ET treatment cycle during January,2008and December,2010in our hospital were selected for this retrospective study.They all experienced a poor ovarian response(less than 5oocytes retrieved)on their first attempt with conventional therapy,and then received individualized treatment on the second cycle.The patients were assigned into 2 groups by ovarian response during the two cycles:group A (104cases),oocytes retrieved<5in both 1st and 2nd cycles; group B (135cases),oocytes retrieved<5in the 1st cycle,but≥5in the 2nd cycle.The protocols and outcomes of the two cycles of these groups were compared.Results The protocols of the 2nd cycle of the two groups demonstrated principles of individualized treatment:①An increasing proportion of GnRH-a short protocol,mini-stimulation protocol and other protocols were found in the two group,while long-term protocol was decreased [group A,long procotol:8.7%vs 34.6% (P<0.01);mini-stimulation protocol:23.1% vs 8.7% (P<0.01);group B,long procotol:26.7% vs 4 9.6%(P<0.01),shortprotocol:50.4%vs37.8%(P<0.05),otherprotocols:13.3%vs5.9%(P<0.05)].②More growth hormone were applied at the 2nd cycle than those at the 1st cycle:group A,56.7%vs 26.0%(P< 0.05);group B,45.9%vs 17.0% (P<0.01).③ The Gn started dosage at the second cycle in both A and B is higher than that in the first one:group A,(244±101)U vs(218±56)U (P<0.05);group B,(229±68)U vs(204±61)U (P<0.01),and there was no significant difference in the doses of gonadotrophins used and the days of COH in this two groups between the two cycles(P>0.05).④ The peak E2levels on day of hCG administration,follicles>14mm in diameter,oocytes retrieved,the number of high quality embryos and the proportion of cancelled transplantation for poor quality embryos between two cycles were similar in groupA (P>0.05).In the 2nd attempt of group B,the peak E2levels on day of hCG administration,follicles>14mm in diameter,oocytes retrieved,the number of high quality embryos,the number of embryo transferred and the clinical pregnancy rate were significantly higher than the 1st cycle[(10 789.8±6 246.3)pmol/L vs.(6 595.0±4 470.1)pmol/L,7.1±3.9vs 4.3±2.5,8.1±3.5vs 3.0±1.1,3.3±2.1vs 1.5±1.1,2.6±0.6vs 2.0±0.7,40.3%vs 11.6%,P<0.01], and the proportion of cancelled cycles due to poor quality embryos was significantly lower than those in the 1st cycle (8.1%vs 25.9%,P<0.01).Conclusions All the poor responders with conventional protocols at their first cycles could get better clinical results at their second cycles,by the formulation of individual treatment therapy,such as an increasing Gn started dosage,more GnRH-a short protocol and mini-stimulation protocol and the application of growth hormone,although 43.5%of the patients still got poor ovarian response.