多囊卵巢综合征患者体外受精/卵胞质内单精子显微注射周期中拮抗剂和全程克罗米芬方案的妊娠结局比较

Comparison of pregnancy outcomes using gonadotrophin-releasing hormone antagonists and clomiphene citrate mild stimulation approaches in in vitro fertilization patients with polycystic ovary syndrome

目的比较对多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者进行体外受精/单精子卵胞质内注射(in vitro fertilization/intracytoplasmic sperm injection,IVF/ICSI)辅助生殖技术助孕时,使用拮抗剂或全程克罗米芬(CC)的温和刺激方案促排卵的妊娠结局及风险。方法回顾性队列分析2014年1月—2015年12月期间接受IVF/ICSI助孕的PCOS患者,符合纳入标准的共361个取卵周期,其中拮抗剂方案224个周期,全程CC方案137个周期。比较使用2种不同卵巢刺激方案每取卵周期的累积活产率(cumulative live birth rate,CLBR)、获卵数、促性腺激素(Gn)用量及刺激时间、受精率、优质胚胎率和卵巢过度刺激综合征(OHSS)的发生率。结果拮抗剂方案的CLBR为75.4%,高于全程CC方案的64.2%,差异有统计学意义(P=0.022)。全程CC方案组的促性腺激素使用总剂量[1 140.5±474.8)IU]及刺激时间[(9.4±1.8)d]显著少于拮抗剂方案组[(1 380.7±498.1)IU,(10.1±2.3)d](P=0.000,P=0.002),h CG注射日内膜厚度[(8.5±2.2)mm]低于拮抗剂方案组[(10.0±1.9)mm](P=0.000)。两组的获卵数和受精率无显著性差异(P>0.05),但拮抗剂方案的优质胚胎率[78.4%(1 285/1 639)]高于全程CC方案[71.6%(643/898)](P=0.000)。拮抗剂方案的中重度OHSS的发生率为8.9%,高于全程CC方案组的5.1%,但差异无统计学意义(P>0.05)。结论 PCOS患者进行IVF/ICSI助孕使用不同的温和刺激方案时,拮抗剂方案的CLBR和优质胚胎率较全程CC方案更高,但是全程CC方案的药物用量更低,OHSS的风险降低。全程CC方案在高反应人群中的应用价值,还需要更大样本的前瞻性随机对照研究来得出结论。

Objective To validate the use of clomiphene citrate （CC） in in vitro fertilization/ intracyroplasmic sperm injection-embryo transfer （IVF/ICSI-ET） when mild stimulation approaches are chosen compared with gonadotrophin-releasing hormone antagonist （GnRH-A） approaches in patients with polycystic ovary syndrome （PCOS）. Methods Of the PCOS patients who underwent IVF/ICSI from January 1, 2014 to December 31, 2015 in our reproductive center, a total of 361 oocytes retrieved cycles were included, among them, 224 cycles were stimulated using the antagonist protocol while 137 cycles were stimulated with CC and gonadotropin （Gn）. The clinical and laboratory parameters of different ovarian stimulation protocols were analyzed. Results The cumulative live birth rate （CLBR） of antagonist group （75.4%） was significantly higher than that of clomiphene-based protocol （64.2%） （P=0.022）. Compared with antagonist protocol, the amount of Gn used （P=0.000） and stimulation day （P=0.002） of clomiphene-based cycles were significantly lower. The endometral thickness on the day of human chorionic gonadotropin （hCG） trigger was thinner than that of antagonist protocol （P=0.000）. Although the number of oocytes retrieved and fertility rate were non significantly higher, the good-quality embryo rate was higher in the antagonist protocol compared with the clomiphene-based protocol. The incidence rate of OHSS in clomiphene group （5.1%） was slightly lower than that of antagonist protocol （8.9%）, in spite of no significant difference was found. Conclusion Medication cost per cycle for clomiphene group were significantly less, but it should be viewed in the context of reduced CLBR. Whether mild stimulation using CC in combination with low dose of Gn used can be considered a realistic option for good- prognosis patients undergoing IVF still questioned.