适当延长GnRH-a降调节时间对卵泡发育同步性的影响

Appropriate prolongation of GnRH-a down-regulation improves the synchronism of follicular development

目的:通过比较绒毛膜促性腺激素释放激素激动剂(GnRH-a)降调节时间的不同对卵泡直径、子宫内膜厚度以及血卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)水平的影响,从而寻求体外受精-胚胎移植(IVF-ET)超促排卵相对合适的启动时间。方法:选择2009年在我中心进行IVF-ET的患者42例,全部采用黄体中期GnRH-a降调节的长方案。①根据GnRH-a降调节时间的不同分为降调节10、15、18 d 3组,分别进行B超监测卵泡的直径、子宫内膜厚度,抽血测定FSH、LH、E2水平,比较降调节时间的不同对卵泡直径、内膜厚度、性激素水平的影响。②降调节后的1、7、10、14 d,分别比较注射GnRH-a前以及注射后2、3 h血FSH、LH的变化。结果:①降调节10、15、18 d不同直径卵泡所占百分比:3～4 mm:16.8%vs 7.09%vs 10.38%;4.5～7.0 mm:80.24%vs89.55%vs 84.62;7.5～10 mm:2.96%vs 3.36%vs 5%。3～4 mm直径的卵泡在降调节10 d所占比例,与15、18 d有显著差异(P<0.05);4.5～7 mm直径的卵泡在15 d所占比例与10、18 d有显著差异(P<0.05);②降调节10、15、18 d内膜厚度(mm):7.73±2.48 vs 5.41±0.79 vs 5.24±0.85,降调节10 d内膜明显厚于15、18 d,有显著差异(P<0.05);③降调节10、15、18 d血FSH(mIU/ml):3.70±1.10 vs 3.51±0.72 vs 3.47±0.61;血LH(mIU/ml):1.23±1 vs 1.09±0.47 vs 1.22±0.72;E2:41.84±36.81 vs 32.84±14.32 vs 9.50±8.23,无显著差异。研究2:降调节后的1、7、10、14 d,注射GnRH-a后2、3 h,血FSH、LH都有升高,其中D1 d升高幅度最大,1.87±1.49 vs 13.33±7.81;1.06±1.13 vs 47.40±29.97,有统计学差异(P<0.05)。结论:在IVF-ET超促排卵长方案中,当GnRH-a降调节10 d,子宫内膜厚度、血FSH、LH、E2已趋于稳定,无很大波动;而卵泡直径在降调节15 d,4.5～7.0 mm的卵泡所占比例较10 d组增加,继续降调节至18 d,该组卵泡数并不增多,但3～4 mm的小卵泡数有所增加。因此,适当延长GnRH-a降调节时间可以改善卵泡发育的同步性。

Objective： To determine the relatively appropriate actuation time for ovarian super-stimulation of IVF-ET by comparing the influences of different down-regulation days of ehorionie gonadotrophin releasing hormone agonist （GnRH-a） upon the follicular diameter, endometrial thickness and the levels of follicle- stimulating hormone （FSH）, luteinizing hormone （LH） and estradiol （E2）. Methods ： We adopted the long protocol of GnRH-a down-regulation in the midluteal phase for 42 patients undergoing IVF-ET. According to the time of GnRH-a down-regulation, we divided the patients into a 10 d, a 15 d and an 18 d group, measured their follicular diameters and endometrial thickness by B-mode ultrasonography, detected the levels of FSH, LH and E2 in the blood, and analyzed the influences of different days of GnRH-a down-regulation on the follicular diameter, endometrial thickness and sexual hormone levels. At 1, 7, 10 and 14 d of down-regulation, we compared the levels of FSH and LH in the blood before the injection of GnRH-a with those 2 and 3 h after it. Results： At 10, 15 and 18 d after down-regulation, the ovarian follicles with the diameter of 3 -4 mm ac- counted for 16.8, 7.09 and 10.38% （P 〈 0.05, 10 d vs 15 d and 18 d） , those with the diameter of 4.5 - 7.0 mm made up 80.24, 89.55 and 84.62% （ P 〈0.05, 15 d vs 10 d and 18 d）, and those with the diameter of 7.5 - 10 mm constituted 2.96, 3.36 and 5% , respectively. Endometrial thickness was （7.73 ±2.48） mm in the 10 d group, significantly thicker than （5.41±0.79） mm and （ 5.24 ± 0.85） mm in the 15 d and 18 d groups （P 〈 0.05）. The FSH levels in the 10 d, 15 d and 18 d groups were （3.70± 1.10） , （3.51±0.72） and （3.47 ±0.61） mlU/ml, the LH levels were （1.23±1.00） , （1.09 ±0.47） and （1.22 ±0.72） mlU/ml, and the E2 levels were 41.84 ± 36.81, 32.84 ± 14.32 and 9.50 ± 8.23, respectively, with no significant differences among the three groups. At 1, 7, 10 and 14 d of down-regulation, both FSH and LH levels in the blood were increased at 2 and 3 h after GnRH-a injection, most significantly at 1 d （1.87±1.49 vs 13.33±7.81 for FSH, 1.06 ±1.13 vs47.40±29.97 for LH, （P〈0.05）. Conclusion ： In the long protocol of ovarian super-stimulation of IVF-ET, endometrial thickness and the levels of FSH, LH and E2 tended to be stable at 10 d of GnRH-a down-regulation. The percentage of the follicles with the diameter of 4.5 - 7.0 mm was higher at 15 d than at 10 d, but rose no more at 18 d except for an increased number of smaller follicles 3 -4 mm in diameter. Therefore, appropriate prolongation of GnRH-a down-regulation can improve the synchronism of follicular development.