卵巢低反应患者微刺激促排卵取卵后继续黄体期促排卵的临床效果观察

Clinical effect of ovarian stimulation during continuous luteal phase after mini-stimulation protocol in patients with poor ovarian response

目的探讨接受体外受精/卵胞质内单精子显微注射-胚胎移植(IVF/ICSI-ET)的卵巢低反应(POR)患者在卵泡期微刺激方案促排卵取卵后继续行黄体期促排卵的临床效果。方法回顾性分析2016年6月—2017年12月期间在郑州大学第三附属医院行IVF/ICSI-ET助孕的卵巢低反应患者,共144例。所有患者均接受卵泡期微刺激方案促排卵(微刺激组),取卵后继续进行黄体期促排卵(黄体期组)。根据男方精液情况选择IVF或ICSI,所得可利用胚胎全部冷冻,下一周期行冻融胚胎移植,比较2种促排卵方案的临床和实验室指标及移植结局。结果①黄体期组人绒毛膜促性腺激素(hCG)注射日雌二醇水平[(1043.28±744.77)ng/L]和孕酮水平[(6.29±0.73)IU/L]均较微刺激组[(672.47±586.67)ng/L,(1.21±0.94)IU/L]高,hCG注射日促黄体生成素(LH)水平[(3.74±2.93)IU/L]较微刺激组[(8.45±5.81)IU/L]低,差异均有统计学意义(P均<0.001);黄体期组和微刺激组的促性腺激素(Gn)用量[(2117.85±1047.26)IU,(2213.64±877.03)IU]和促排卵时间[(7.76±3.56)d,(8.03±2.63)d]差异无统计学意义(P>0.05)。②微刺激组和黄体期组中的获卵数均呈非正态分布,获卵数为0~1、2~3、>3的例数分别为70比45、53比64、21比35。应用非参数秩和检验,结果显示黄体期组的获卵数较微刺激组高,差异有统计学意义(P=0.022)。可移植胚胎数[1.0(0.0,2.0)比1.0(0.0,2.0)]、双原核(2PN)受精率(70.7%,65.3%)、优质胚胎率(40.3%,38.9%)、未获卵率(13.9%,16.0%)及提前排卵率(6.3%,9.0%)在两种方案中差异均无统计学意义(P>0.05)。③两组患者的移植胚胎数、临床妊娠率和流产率组间比较差异均无统计学意义(P>0.05)。结论POR患者在卵泡期微刺激促排卵后继续行黄体期促排卵可获得更多的卵子,增加可利用胚胎数,提高累积妊娠率。此外,黄体期促排卵方案的hCG注射日LH水平较低,说明黄体期的高孕激素水平起到了明显的降调节作用,是一种安全可行的促排卵方案。

Objective To observe the effect of ovarian stimulation during continuous luteal phase after mini-stimulation protocol in patients with poor ovarian response (POR) receiving in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET). Methods A study of 144 cases following IVF/ICSI-ET was performed in the Third Affiliated Hospital of Zhengzhou University from June 2016 to December 2017. All patients received mini-stimulation regimen (mini-stimulation group). After ovulation, continuous luteal phase stimulation was performed (luteal phase group). According to the semen condition of the male, IVF or ICSI was selected. All the available embryos could be frozen and transferred in the next cycle. The clinical and laboratory indicators and pregnancy outcomes of the two ovulation-promoting protocols were compared. Results 1) In the luteal phase group, the estradiol [(1 043.28±744.77) ng/L vs.(672.47±586.67)ng/L] and progesterone levels [(6.29±0.73) IU/L vs.(1.21±0.94) IU/L] on the human chorionic gonadotropin (hCG) injection day were higher than those of the mini-stimulation group, and the luteinizing hormone (LH) levels on the hCG injection day [(3.74±2.93) IU/L vs.(8.45±5.81) IU/L] were lower than those of the mini-stimulation group, differences were statistically significant (P<0.001). Between luteal phase group and mini-stimulation group, there were no significant differences in gonadotropin (Gn) used dosage [(2 117.85±1 047.26) IU/L vs.(2 213.64±877.03) IU/L] and ovulation days [(7.76±3.56) d vs.(8.03±2.63) d](P>0.05). 2) The number of retrieved oocytes in the mini-stimulation group and the luteal phase group presented a non-normal distribution, which was expressed by the median and quartile spacing. The number of retrieved oocytes were divided into 0-1, 2-3,>3, and the corresponding cases were 70 vs. 45, 53 vs. 64, 21 vs. 35. Non-parametric rank sum test was applied, and the results showed that the number of retrieved oocytes in the luteal phase group was higher than that in the mini-stimulation group, and the difference was statistically significant (P=0.022). Available embryos [1.0(0.0,2.0) vs. 1.0(0.0,2.0)], two pronucleus (2PN) fertilization rate (70.7% vs. 65.3%), high-quality embryo rate (40.3% vs. 38.9%), premature ovulation rate (6.3% vs. 9.0%) were not statistically different between the two protocols (P>0.05). 3) The number of transplanted embryos (1.53±0.51 vs. 1.57±0.54), the clinical pregnancy rate (18.4% vs. 28.3%) and the miscarriage rate (22.2% vs. 23.5%) were not statistically different between the two groups (P>0.05). Conclusion Patients with POR can obtain more oocytes, increase available embryos and promote cumulative pregnancy rate. Moreover, the lower level of LH on the hCG injection day during luteal phase ovarian stimulation indicated that the high progesterone level in the luteal phase plays a significant role in down regulation, which is a safe and feasible program.