体外受精患者卵巢反应不良后续治疗方案的比较

Comparison of different stimulation protocols for patients receiving in vitro fertilization after poor ovarian response

目的研究体外受精首个治疗周期卵巢反应不良（POR）后，后续周期采用不同治疗方案的疗效比较。方法2011年1月至2012年7月本中心黄体中晚期长方案时出现卵巢反应不良患者174例，分析首个体外受精一胚胎移植（IVF—ET）周期的临床资料；后续（第2周期）使用促排卯方案的80个周期分4组（长方案组、拮抗剂方案组、短方案组及微刺激方案组），比较4组的治疗结果，以及49例卵巢反应不良与16例未达到欧洲人类生殖和胚胎学协会标准的后续治疗的卵巢反应情况。结果首个周期，174例总妊娠率为26．1％，4个年龄段（≤30岁、31～35岁、36～40岁、t〉41岁）妊娠率为21．1％（4／19）、37．9％（11／29）、32．1％（9／28）、0（0／16），差异有统计学意义（P〈O．05）。第2周期，4组基础卵泡刺激素（bFSH）、基础实卵泡数（AFC）、卵子总数、成熟卵子数、可利用胚胎数、优质胚胎数以及移植胚胎数的差异均有统计学意义（均P〈O．05）。微刺激组的促性腺素（Gn）用量以及使用Gn天数比其他3组明显减少（P〈0．05）。优质胚胎率、移植优质胚胎数、周期取f肖率、移植周期妊娠率与持续妊娠率4组间差异无统计学意义（P〉O．05）。4组的总优质胚胎率（14．9％、25．4％、32．0％、36．8％）差异无统计学意义（P〉O．05）。4例早期流产，均为拮抗剂方案组。POR后此类病例再次POR发生率是36．9％。POR组再次POR的发生率为46．9％。偶发POR组，后续周期卵巢正常反应率达到93．8％。两组的不良反应率差异有统计学意义（P〈0．05）。结论年轻、卵巢储备功能尚好的卵巢反应不良患者可选用长方案。高龄、卵巢储备功能较差的卵巢反应不良患者可选用微刺激方案或短方案。POR诊断标准有助于筛选偶发POR患者。

Objective To compare the outcomes of different stimulation protocols in pahents who showed poor ovarian response （POR） following the initial in vitro fertilization. Methods We analyzed the clinical profiles of 174 patients who had POR during the initial prolonged gonadotrop!!l-releasing hormone （GnRH） cycle of in vitro fertilization-embryo transplantation were analyzed. Eighty patients who received subsequent therapy were allocated to different protocol treatment groups, namely prolonged GnRH treatment, GnRH antagonist, shortened GnRH treatment and micro-stimulation protocol, for comparison on the efficacy. The ovarian responses in the second cycle of 49 patients fi＇om POR group and 16 patients who did not merit the ESHRE criteria were also analyzed. Results In the first cycle, the pregnancy rate was 26.1% in total and 21.1% （4/19） , 37.9% （11/29） , 32.1% （9/28） and 0 （0/16） in ≤30, 31-35, 36-40 and 341 years groups, respectively （P〈0.05）. In the second cycle, the between-group differences in baseline follicularstimulating hormone, AFC, number of oocytes and mature oocytes, the embryos available, the embryos of high quality and for transplantation were all significant （all P〈0.05）. Reduced total gonadotropin （Gn） doses and the duration of stimulation was noted in micro-stimulation group when compared with other groups （all P〈 0.05）. Contrarily, there were no marked between-group differences in the rates of high-quality embryo and that for transplantation, cancellation, pregnancy, on-going pregnancy and total rate of high-quality embryo （14.9% vs 25.4% vs 32.0% vs 36.8% ） （all P〉0.05）. Four patients, allocated to GnRH antagonist group, presented premature miscarriage. The risk of developing POR was 36.9% in the second cycle and 46.9% in POR group. A normal response rate of 93.8% was found in the subsequent cycles of occasional POR group. The adverse response rate differed considerably between POR and occasional POR groups （P〈O.05）. Conclusions Prolonged GnRH protocol is recommened for POR patients of young age and having normal ovarian reserve, while micro-stimulation or shortened GnRH protocol may be preferable for patients of elder age and with diminished ovarian reserve. The diagnostic criteria of POR may assist the screening of patients with occasional POR.