他莫昔芬与粒细胞集落刺激因子改善难治性薄型子宫内膜患者子宫内膜容受性的临床观察

Clinical study of tamoxifen and granulocyte colony stimulating factor to improve endometrial receptivity in patients with refractory thin endometrium

目的探讨他莫昔芬与粒细胞集落刺激因子(granulocyte colony stimulating factor,G-CSF)治疗难治性薄型子宫内膜患者的临床疗效。方法采用前瞻性队列研究,选取2019年12月至2020年12月期间在昆明医科大学第二附属医院生殖医学科接受冻融胚胎移植(frozen-thawed embryo transfer,FET)周期助孕患者,既往新鲜周期中因内膜不达标而取消移植后再次予雌激素治疗子宫内膜厚度仍<7 mm的患者。经患者知情同意,根据患者自身意愿分为3组:A组他莫昔芬治疗(n=40),B组宫腔灌注G-CSF治疗(n=38),C组他莫昔芬联合宫腔灌注G-CSF治疗(n=36)。比较3组患者子宫内膜容受性相关指标及临床结局。结果3组患者一般情况及治疗前子宫内膜厚度差异均无统计学意义(均P>0.05)。治疗后子宫内膜厚度A组[8.00(8.00,9.00)mm]和C组[8.00(8.00,10.00)mm]显著大于B组[7.00(7.00,8.00)mm,P=0.002,P=0.001],3组患者治疗后子宫内膜厚度均有增加,差异均有统计学意义(均P<0.001)。C组Ⅲ型血流占比为72.2%(26/36),显著高于A组和B组[40%(16/40),P=0.005;42.1%(16/38),P=0.009]。子宫内膜血流阻力指数(resistance index,RI)、搏动指数(pulsatility index,PI)和收缩期峰值血流速度/舒张末期血流速度比值(systolic peak velocity/diastolic velocity,S/D)B组(0.61±0.08、0.81±0.11、2.05±0.12)和C组(0.60±0.11、0.78±0.15、1.99±0.19)显著低于A组(0.66±0.04、0.94±0.10、2.17±0.06),差异均有统计学意义(RI:P=0.009,P=0.001;PI:P<0.001,P<0.001;S/D:P<0.001,P<0.001)。C组胚胎种植率和临床妊娠率较A组、B组有增高趋势,早期流产率有下降趋势,但组间差异均无统计学意义(均P>0.05)。结论3种治疗方案对改善难治性薄型子宫内膜患者子宫内膜容受性以及妊娠结局均有一定疗效,其中他莫昔芬联合G-CSF治疗在改善子宫内膜容受性方面优于单一用药,但在妊娠结局中联合用药尚未体现出显著优势。

Objective To investigate the clinical efficacy of tamoxifen and granulocyte colony stimulating factor(G-CSF)in the treatment of refractory thin endometrium.Methods Prospective cohort study was performed.Patients treated in the Department of Reproductive Medicine of the Second Affiliated Hospital of Kunming Medical University from December 2019 to December 2020 were included,they all suffered from cancellation of fresh transplantation cycle due to endometrial thickness less than 7 mm,and estrogen treatment was given in the following frozen-thawed embyro transfer cycle but the thickness of endometrium still under 7 mm.They were divided into three groups according to their wishes:group A was treated with tamoxifen(n=40),group B was treated with intrauterine perfusion of G-CSF(n=38),and group C was treated with tamoxifen combined with intrauterine perfusion of G-CSF(n=36).The endometrial receptivity and pregnancy outcomes among the three groups were compared.Results There were no significant differences in the clinical characteristics of patients and the thickness of endometrium before treatment among the three groups(all P>0.05).The endometrial thickness after treatment was significantly improved compared with those before treatment among the three groups(P<0.001).After treatment,endometrial thickness of group A[8.00(8.00,9.00)mm]and group C[8.00(8.00,10.00)mm]was higher than that of group B[7.00(7.00,8.00)mm,P=0.002,P=0.001].The type ofⅢendometrial blood flow of group C[72.2%(26/36)]was significantly improved compared with group A[40.0%(16/40),P=0.005)]and group B[42.1%(16/38),P=0.009].The resistance index(RI),pulsatility index(PI)and systolic peak velocity/diastolic velocity(S/D)of group B(0.61±0.08,0.81±0.11,2.05±0.12)and group C(0.60±0.11,0.78±0.15,1.99±0.19)were lower than those of group A(0.66±0.04,0.94±0.10,2.17±0.06),and the differences among the three groups were statistically significant(RI:P=0.009,P=0.001;PI:P<0.001,P<0.001;S/D:P<0.001,P<0.001).The embryo implantation rate and the clinical pregnancy rate of group C were higher than those of group A and group B,and the early abortion rate of group C was lower than that of group A and group B,but there were no significant differences among the three groups(all P>0.05).Conclusion Three treatment schemes have certain curative effects on improving the endometrial receptivity and pregnancy outcome of patients with refractory thin endometrium,among which tamoxifen combined with G-CSF is superior to single drug in improving the endometrial receptivity,but the combined group has not shown significant advantages in pregnancy outcome.