来曲唑序贯治疗来曲唑促排卵失败多囊卵巢综合征的疗效观察

Clinical observation of letrozole sequential therapy in treatment of polycystic ovary syndrome due to letrozole induced ovulation failure

目的探讨来曲唑序贯治疗来曲唑促排卵失败多囊卵巢综合征的临床疗效。方法选取2016年12月—2018年3月在天津医科大学第二医院计划生育科就诊的来曲唑促排卵失败的178例多囊卵巢综合征患者为研究对象,共234个促排周期。按照随机数字表将发生来曲唑促排卵失败的178例多囊卵巢综合征患者随机分为来曲唑序贯来曲唑组(62例,共87个周期)、来曲唑序贯氯米芬组(59例,共75个周期)和来曲唑序贯尿促性素组(57例,共72个周期)。3组患者均在月经第5天口服来曲唑片5mg/次,1次/d,停药第3天监测卵泡,卵泡直径≤10mm的患者用药。来曲唑序贯来曲唑组患者口服来曲唑片,5 mg/次,1次/d,连续5 d,停药后第1天行阴道超声检查。来曲唑序贯氯米芬组患者口服枸橼酸氯米芬片,100mg/d,连续5d,停药后第1天行阴道超声检查。来曲唑序贯尿促性素组患者肌内注射注射用尿促性素,75U/d,根据卵泡反应调整剂量,直到出现优势卵泡。比较3组患者的单卵泡率、排卵率、周期取消率和失败率;人绒毛膜促性腺激素日子宫内膜的厚度和类型;临床妊娠率、早期胚胎丢失率、多胎妊娠率和卵巢过度刺激综合征发生率;促排方案中序贯用药的时间、费用和患者对促排卵方案的满意度。结果治疗后,来曲唑序贯来曲唑组、来曲唑序贯氯米芬组的单卵泡发育率显著高于来曲唑序贯尿促性素组,且来曲唑序贯来曲唑组的单卵泡发育率显著高于来曲唑序贯氯米芬组,3组间差异均有统计学意义(P<0.05)。治疗后,来曲唑序贯来曲唑组、来曲唑序贯尿促性素组的排卵率均高于来曲唑序贯氯米芬组,差异有统计学意义(P<0.05)。治疗后,来曲唑序贯来曲唑组、来曲唑序贯氯米芬组的周期取消率显著低于来曲唑序贯尿促性素组,且来曲唑序贯来曲唑组的周期取消率显著低于来曲唑序贯氯米芬组,3组间差异均有统计学意义(P<0.05)。治疗后,来曲唑序贯来曲唑组、来曲唑序贯尿促性素组子宫内膜厚度明显厚于来曲唑序贯氯米芬组(P<0.05)。治疗后,来曲唑序贯来曲唑组、来曲唑序贯氯米芬组的多胎妊娠率显著低于来曲唑序贯尿促性素组,且来曲唑序贯来曲唑组的多胎妊娠率显著低于来曲唑序贯氯米芬组,3组间差异均有统计学意义(P<0.05)。治疗后,来曲唑序贯来曲唑组、来曲唑序贯氯米芬组的卵巢过度刺激综合征发生率低于来曲唑序贯尿促性素组,差异有统计学意义(P<0.05)。来曲唑序贯来曲唑组、来曲唑序贯氯米芬组明显短于来曲唑序贯尿促性素组的用药时间(P<0.05)。来曲唑序贯尿促性素组的总费用显著高于来曲唑序贯氯米芬组、来曲唑序贯来曲唑组。患者对来曲唑序贯来曲唑组、来曲唑序贯氯米芬组的促排卵方案满意度高。结论来曲唑序贯来曲唑方案具有较高的排卵率、妊娠率,同时多胎妊娠率、卵巢过度刺激综合征风险最低,不但减少了肌内注射尿促性素多卵泡发育的风险,而且方案更加简单方便,节省患者的时间和花费,是一种既经济有效又安全省时的促排卵方案,非常适合全科医生在基层医疗机构中推广应用。

Objective To evaluate the clinical effect of letrozole sequential therapy in treatment of polycystic ovary syndrome due to letrozole induced ovulation failure. Methods Patients(178 cases) with polycystic ovary syndrome due to letrozole induced ovulation failure in the Second Hospital of Tianjin Medical University from December 2016 to March 2018 were randomly divided into letrozole sequential letrozole group(62 cases, 87 cycles), letrozole sequential clomiphene group(59 cases, 75 cycles), and letrozole sequential gonadotropin group(57 cases, 72 cycles). All the three groups were po administered with Letrozol Tablets on the fifth day of menstruation, 5 mg/time, once daily. And the follicles were monitored on the third day after drug withdrawal, if the follicle diameter of the patient was less than or equal to 10 mm, and medication was given. Patients in letrozole sequential letrozole group were po administered with Letrozol Tablets, 5 mg/time, once daily, continuous treatment for 5 d, and vaginal ultrasound examination was performed on the first day after drug withdrawal. Patients in letrozole sequential clomiphene group were treated with clomiphene citrate tablets, 100 mg/d, continuous treatment for 5 d, and vaginal ultrasound examination was performed on the first day after drug withdrawal. Patients in letrozole sequential gonadotropin group were iv administered with Menotrophins for injection, 75 U/d, and the dosage was adjusted according to the follicular response until dominant follicles appeared. The follicular development, the cycle cancellation rate and failure rate, the endometrial thickness and type on human chorionic gonadotropin day, the pregnancy outcome, the clinical pregnancy rate, the early embryo loss rate, the multiple pregnancy rate, the ovarian hyperstimulation syndrome incidence rate, the time and cost of sequential medication, and the satisfaction of ovulation induction program among three groups were compared. Results After treatment, the single follicle development rate of letrozole sequential letrozole group and letrozole sequential clomiphene group was significantly higher than that of letrozole sequential gonadotropin group, and the single follicle development rate of letrozole sequential letrozole group was significantly higher than that of letrozole sequential clomiphene group, and the differences among the three groups were statistically significant(P < 0.05). After treatment, the ovulation rate of letrozole sequential letrozole group and letrozole sequential gonadotropin group were higher than that of letrozole sequential clomiphene group, and the difference was statistically significant(P < 0.05). After treatment, the cycle cancellation rate of letrozole sequential letrozole group and letrozole sequential clomiphene group was significantly lower than that of letrozole sequential gonadotropin group, and the cycle cancellation rate of letrozole sequential letrozole group was significantly lower than that of letrozole sequential clomiphene group, and the differences among the three groups were statistically significant(P < 0.05). After treatment, the endometrial thickness in letrozole sequential letrozole group and letrozole sequential gonadotropin group was significantly thicker than that of letrozole sequential clomiphene group(P < 0.05). After treatment, the multiple pregnancy rate of letrozole sequential letrozole group and letrozole sequential clomiphene group was significantly lower than that of letrozole sequential gonadotropin group, and the multiple pregnancy rate of letrozole sequential letrozole group was significantly lower than that of letrozole sequential clomiphene group, and the differences among the three groups were statistically significant(P < 0.05). After treatment, the incidence of ovarian hyperstimulation syndrome in letrozole sequential letrozole group and letrozole sequential clomiphene group was lower than that in letrozole sequential gonadotropin group(P < 0.05). The medication time of letrozole sequential letrozole group and letrozole sequential clomiphene group were significantly shorter than letrozole sequential gonadotropin group(P < 0.05). The total cost of letrozole sequential gonadotropin group was significantly higher than that of letrozole sequential clomiphene group and letrozole sequential letrozole group. Patients with letrozole sequential letrozole group and letrozole sequential clomiphene group were highly satisfied with ovulation induction. Conclusion Letrozole sequential letrozole regimen has higher ovulation rate and pregnancy rate, while the risk of multiple pregnancy rate and ovarian hyperstimulation syndrome is the lowest. It not only reduces the risk of multiple follicle development by intramuscular Menotrophins for injection, but also is more simple and convenient, saving time and cost for patients, which is an economical, effective, safe, and time-saving ovulation induction program, and it is very suitable for general practitioners to promote their application in primary medical institutions.