滋阴补阳中药序贯法联合rFSH低剂量递增方案治疗CC抵抗的临床观察

Clinical observation on the effect of sequential method of nourishing Yin and tonifying Yang combined with rFSH low-dose step-up protocol in treatment of clomiphene resistance

目的探讨滋阴补阳中药序贯法联合重组人促卵泡激素(recombinant human follicle stimulating hormone,r FSH)低剂量递增方案治疗克罗米芬(clomiphene citrate,CC)抵抗的有效性和安全性。方法将60例CC抵抗的不孕症患者随机分为试验组(30例,采用滋阴补阳中药序贯法联合r FSH低剂量递增方案)和对照组(30例,采用r FSH低剂量递增方案),观察两组患者周期排卵率、单卵泡排卵率、周期取消率、卵巢过度刺激综合征(ovarian hyperstimulation syndrome,OHSS)发生率、注射h CG日子宫内膜厚度和形态、周期妊娠率、累积妊娠率、流产率、双胎妊娠率、多胎妊娠率、r FSH阈值量、使用时间和总用量。两组患者经过3个治疗周期后进行血、尿常规及肝肾功能检查。结果试验组共完成58个治疗周期,对照组共完成50个治疗周期。两组单卵泡排卵率经比较有统计学差异(P<0.05);两组注射h CG日子宫内膜厚度经比较有统计学差异(P<0.01);两组流产率经比较有统计学差异(P<0.05);两组r FSH阈值量经比较有统计学差异(P<0.05);两组r FSH使用时间和r FSH总用量经比较有统计学差异(P<0.01)。两组周期排卵率、周期取消率、OHSS发生率、注射h CG日A级子宫内膜、周期妊娠率、累积妊娠率、双胎妊娠率经比较无统计学差异(P>0.05)。两组无多胎妊娠发生。两组血、尿常规及肝肾功能未见异常,无不良反应发生。结论滋阴补阳中药序贯法联合r FSH低剂量递增方案治疗CC抵抗患者,与单纯的r FSH低剂量递增方案相比,在获得相似的、可接受的排卵率、妊娠率、周期取消率的同时,缩短了优势卵泡发育时间和治疗时间,更有利于单卵泡排卵;增加了注射h CG日子宫内膜厚度,降低了早期流产率,减少了r FSH总用量,降低了治疗费用;治疗期间OHSS和双胎发生率控制在可接受的范围内,未出现严重不良反应,是一种安全、有效的治疗CC抵抗的方案。

Objective To explore the efficacy and security of sequential method of nourishing Yin and tonifying Yang combined with recombinant human follicle stimulating hormone （rFSH） low-dose step-up protocol in treatment of clomiphene （CC） resistance. Methods Sixty CC-resistant infertile patients were randomly divided into experimental group and control group, 30 patients in experimental group were treated by sequential method of nourishing Yin and tonifying Yang combined with rFSH low-dose step-up protocol, while 30 patients in control group were treated by rFSH low-dose step-up protocol The cycle ovulation rates, monoovulation rates, cycle cancellation rates, incidence rates of ovarian hyperstimulation syndrome （OHSS） , the endometrial thicknesses and morphology on human chorionic gonadotropin （hCG） injection day, cycle pregnancy rates, cumulative pregnancy rates, abortion rates, twin pregnancy rates, multiple pregnancy rates, rFSH threshold doses, rFSH usage time and total doses in the two groups were observed. Blood routine examination, urinary routine examination, hepatic function test, and renal function test were conducted after three treatment cycles in the two groups. Results The patients in experimental group completed 58 treatment cycles, meanwhile, the patients in control group completed 50 treatment cycles. There was statistically significant difference in mono-ovulation rate between the two groups （ P〈0.05 ） ; there was statistically significant difference in endometrial thickness on hCG injection day between the two groups （P〈0. 01 ） ; there was statistically significant difference in abortion rate between the two groups （P〈0.05） ; there was statistically significant difference in rFSH threshold dose between the two groups （P〈0. 05 ） ; there were statistically significant differences in rFSH usage time and total dose between the two groups （ P〈0. 01 ） . There was no statistically significant difference in cycle ovulation rate, cycle cancellation rate, incidence rate of OHSS, grade A endometrium on hCG injection day, cycle pregnancy rate, cumulative pregnancy rate, and twin pregnancy rate between the two groups （P〉0. 05） . No multiple pregnancy occurred. No abnormality was found during blood routine examination, urinary routine examination, hepatic function test, and renal function test, no adverse reaction occurred. Conclusion Compared with simple rFSH low-dose step-up protocol, sequential method of nourishing Yin and tonifying Yang combined with rFSH low-dose step-up protocol can obtain the similar and acceptable cycle ovulation rate, pregnancy rate,and cycle cancellation rate, moreover, it shortens dominant follicular development time and treatment time, which is more beneficial to mono-ovulation, the method increases the endometrial thickness on hCG injection day, reduces early abortion rate, rFSH total dose, and treatment cost. The incidence rates of OHSS and twin pregnancy are controlled within the acceptable range during treatment, no adverse reaction occurs, whieh is a safe and effective method in treatment of CC resistance.