不同剂量注射用醋酸亮丙瑞林微球在体外受精-胚胎移植中的应用

Clinical applications of different doses of leuprorelin acetate in in vitro fertilization-embryo transfer

目的评价不同剂量注射用醋酸亮丙瑞林微球（简称：亮丙瑞林）在体外受精一胚胎移植（IVF-ET）周期中应用的临床效果。方法对2011年1月至12月在安徽医科大学解放军临床学院生殖医学中心接受IVF-ET和（或）卵母细胞胞质内单精子注射一胚胎移植（ICSI-ET）治疗的268例患者的控制性超促排卵周期的临床资料进行回顾性分析。按照降调节药物种类及剂量分为3组，亮丙瑞林低剂量组：亮丙瑞林1．25mg，共83个周期；亮丙瑞林高剂量组：亮丙瑞林1．88mg，共68个周期；注射用醋酸曲普瑞林（简称：曲普瑞林）组：曲普瑞林1．25mg，共117个周期；均采用黄体期长方案降调节并行超促排卵，比较3组患者年龄、降调节后月经周期第3～5天、促性腺激素（Gn）注射日和hCG注射日血清卯泡刺激素（FSH）、黄体生成素（LH）、雌二醇及孕酮水平，比较3组Gn用量及使用天数、获卵数、成熟卵数、受精率、卵裂率、优质胚胎率、临床妊娠率和流产率。结果3组患者平均年龄、hCG注射日的LH、雌二醇及孕酮水平比较，差异均无统计学意义（P〉0．05）。亮丙瑞林低剂量组、亮丙瑞林高剂量组和曲普瑞林组患者Gn注射日血清FSH水平分别为（3．8±1．6）、（3．1±1．4）和（2．4±1．3）U／L，3组分别比较，差异均有统计学意义（P〈0．05）；Gn使用天数分别为（9．8±1．7）、（10．5±1．8）和（11．1±1．4）d，3组分别比较，差异也有统计学意义（P〈0．05）；Gn用量分别为（24±7）、（27±9）和（28±7）支，亮丙瑞林低剂量组Gn用量显著低于亮丙瑞林高剂量组和曲普瑞林组，分别比较，差异均有统计学意义（P〈0．05）；亮丙瑞林低剂量组、曲普瑞林组患者Gn注射日血清LH水平分别为（2．7±1．6）和（2．2±1．0）U／L，两组比较，差异有统计学意义（P〈0．05）。亮丙瑞林低剂量组、亮丙瑞林高剂量组和曲普瑞林组取消移植分别为5、4和7例；获卵数分别为（14±7）、（13±6）和（14±6）个；受精率分别为66．26％（758／1144）、67．01％（589／879）和68．54％（1111／1621）；优质胚胎率分别为64．22％（472／735）、60．50％（340／562）和59．59％（640／1074）；临床妊娠率分别为49％（38／78）、42％（27／64）和50％（55／110）；流产率分别为18％（7／38）、15％（4／27）和15％（8／55）；3组分别比较，差异均无统计学意义（P〉0．05）。结论1．25mg和1．88mg亮丙瑞林均可获得满意的降调节效果和临床结局；1．25mg亮丙瑞林可减少降调节中药物用量及超促排卵过程中Gn的用量和使用时间，降低医疗费用。

Objective To evaluate the clinical effect of different doses of leuprorelin acetate in in vitro fertilization-embryo transfer（IVF-ET）. Methods From January 2011 to December 2011, the data of 268 patients undergoing IVF and （or） intraeytoplasmie sperm injection （ICSI） in Reproductive Medical Center, Clinical College of PLA, Anhui Medical University were studied retrospectively. All the patients were divided into three groups based on with long protocol and controlled ovarian stimulation （COH） including 83 cycles with 1.25 mg of leuprorelin in low dose group, 68 cycles with 1.88 mg of leuprorelin in high dose group, 117 cycles with 1.25 mg of diphereline in control group. The serum follicle stimulating hormone （ FSH）, luteinizing hormone （ LH ）, estradiol （ E2 ） and progesterone （ P ） before gonadotropin （ Gn ）administration on the days 3 - 5 of the menstrual cycle and on the day of hCG administration were detected, the dose and duration of Gn, number of oocytes retrieved, number of mature oocytes, the rates of fertilization, embryo cleaved, good-quality embryos clinical pregnancy and early miscarriage were compared among three groups. Results There were no significant differences in age, the level of LH and P on the day of hCG administration among three groups （P 〉0. 05）. The level of FSH was （3.8 ± 1.6） U/L in low dose leuprorelin group, （3.1 ± 1.4） U/L in high dose of leuprorelin group and （2. 4 ± 1.3 ） U/L in diphereline group before Gn administration, which reached statistical difference （ P 〈 0. 05 ）. The mean length of Gn stimulation were （ 9. 8 ± 1.7 ） days in low dose leuprorelin group, （ 10. 5 ± 1. 8 ） days in high dose of leuprorelin group and （ 11.1 ± 1.4） days in diphereline group, which reached statistical difference （ P 〈 0. 05）. The mean dose of Gn was （24 ± 7） in low dose of leuprorelin group, which was significantly higher than （27 ± 9） in high dose of leuprorelin group and （28 ± 7） in diphereline group （P 〈 0. 05）. The level of LH was （2. 7 ± 1.6） U/L in low dose of leuprorelin group and （2. 2 ± 1.0） U/L in diphereline group before Gn administration, which reached statistical difference（P 〈0. 05）. The cancel cycles were 5 in low dose of leuprorelin group, 4 in high dose of leuprorelin group and 7 in diphereline group. The number of ovum was （14 ± 7） low dose of leuprorelin group, （13 ± 6） in high dose of leuprorelin group, （14 ± 6） in diphereline group. The rates of fertilization was 66. 26% （758/1144） in low dose of leuprorelin group, 67. 01% （589/ 879） in high dose of leuprorelin group and 68.54% （1111/1621 ）in diphereline group, the rates of good- quality embryos was 64. 22% （472/735） in low dose of leuprorelin group,60. 50% （340/562） in high dose of leuprorelin group and 59. 59% （640/1074） in diphereline group, clinical pregnancy was 49% （38/78） in low dose of leuprorelin group, 42% （27/64） in high dose of leuprorelin group and 50% （55/110） in diphereline group, early miscarriage was 18% （7/38）in low dose of leuprorelin group, 15 % （4/27） in high dose of leuprorelin group and 15% （8/55） in diphereline group, which did not show significant differences （P 〉0. 05）. Conclusions Both 1.25 mg and 1.88 mg leuprorelin acetate could obtain good down- regulation effect and clinical outcomes. 1.25 mg leuprorelin acetate could decrease patient＇s costs by reducing Gn dose and duration.