利拉鲁肽提高肥胖不孕多囊卵巢综合征妇女临床妊娠率的研究

目的评价利拉鲁肽与二甲双胍联合用药对减重治疗失败的多囊卵巢综合征(PCOS)不孕患者临床妊娠率及累计妊娠率的影响,同时评价联合用药对卵母细胞和胚胎质量、减重以及代谢和内分泌指数的影响。方法选取2017年6月至2018年12月间在我院治疗的186例减重失败的PCOS肥胖患者。186例患者随机分为联合用药组(联合组)与二甲双胍组,每组93例。二甲双胍组服用二甲双胍片治疗,联合组在二甲双胍组治疗的基础上,加用利拉鲁肽皮下注射治疗,初始剂量为0.6 mg,1次/d,3 d后增加至1.2 mg。所有患者均治疗12周。治疗的同时对所有患者进行积极生活方式干预,干预措施包括控制食物热量及每天进行至少30 min中等强度的身体活动,在药物治疗1个月后给予患者体外受精(IVF)手术,对患者进行12个月随访,记录患者的自然妊娠情况。比较基线期与治疗后患者的人体测量参数、内分泌参数、体脂分布参数及IVF结果。结果治疗后,联合组与二甲双胍组患者体重均较基线期显著降低(t=2.65,P<0.01;t=4.05,P<0.01)。二甲双胍组和联合组患者体重分别下降(5.98±5.03)kg和(7.52±3.90)kg。与二甲双胍组比较,联合组患者体重较基线降低值显著提高(t=2.33,P=0.02)。2组患者内脏脂肪含量、体积和面积均较基线期显著降低(P<0.05)。与二甲双胍组比较,联合组的临床妊娠率(84.0%vs.28.3%,χ^2=30.42,P<0.01)和累计妊娠率(68.8%vs.37.6%,χ^2=18.16,P<0.01)显著提高。两组患者恶心与腹泻发生率比较差异无统计学意义(χ^2=1.56,P=0.21;χ^2=0.58,P=0.45)。结论低剂量利拉鲁肽联合二甲双胍对超重不孕的PCOS患者进行短期干预,可以显著提高患者的临床妊娠率和累计妊娠率,并显著降低PCOS患者的体重、内脏脂肪组织,没有显著增加患者的药物不良反应。

Effect of liraglutide on the clinical pregnancy rate of obese infertile women with polycystic ovary syndrome

Objective To evaluate the effect of combination use of liraglutide with metformin on clinical pregnancy rate and cumulative pregnancy rate in infertile patients with polycystic ovary syndrome(PCOS)who failed in weight loss therapy,and to evaluate the effects of combination therapy on oocyte and embryo quality,weight loss,and metabolic and endocrine indexes.Methods A total of 186 PCOS obese patients who failed in weight loss therapy in our hospital from June 2017 to December 2018 were enrolled.They were randomly divided into combination group and metformin group,with 93 patients in each group.Metformin group was treated with metformin tablets.Combination group was treated with metformin and subcutaneous injection of liraglutide.The initial dose was 0.6 mg once daily,which was increased to 1.2 mg after 3 d.All patients were treated for 12 weeks.Treatment also involved active lifestyle interventions for all patients.The interventions included control of food calories and moderate-intensity physical activity for at least 30 min per day.The surgery of in vitro fertilization(IVF)was given 1 month after drug treatment,and patients were followed for 12 months to record the state of natural pregnancy.The anthropometric parameters,endocrine parameters,and the body fat distribution parameters and IVF results of the patients at baseline and after treatment were compared.Results After treatment,the body weight of combination group and metformin group were significantly lower than that at the baseline value(t=2.65,P<0.01;t=4.05,P<0.01).The body weight of metformin group and combination group decreased(5.98±5.03)kg and(7.52±3.90)kg,respectively.Compared with metformin group,the weight of combination group was more significant(t=2.33,P=0.02).The visceral fat content,volume and area of the two groups were significantly lower than those at the baseline value(P<0.05).Compared with metformin group,the clinical pregnancy rate(84.0%vs.28.3%,χ^2=30.42,P<0.01)and the cumulative pregnancy rate(68.8%vs.37.6%,χ^2=18.16,P<0.01)of combination group were significantly increased.There was no significant difference in the incidence of nausea or diarrhea between the two groups(χ^2=1.56,P=0.21;χ^2=0.58,P=0.45).Conclusion Short-term intervention of low-dose liraglutide combined with metformin for overweight infertile PCOS patients can significantly improve the clinical pregnancy rate and cumulative pregnancy rate,and significantly reduce the weight and visceral fat tissue of PCOS patients,and no significant increase was found in the patient′s adverse drug reactions.