子宫内膜搔刮与宫腔灌注G-CSF对薄型子宫内膜患者行IVF-ET/ICSI后妊娠结局的影响

Effect of endometrial curettage and intrauterine perfusion of G-CSF on pregnancy outcomes after IVF-ET/ICSI in patients with thin endometrium

摘要

目的：比较子宫内膜搔刮、宫腔灌注粒细胞集落刺激因子（granulocyte colony-stimulating factor,G-CSF）单一治疗与联合治疗对薄型子宫内膜（thin endometrium,TE）患者行IVF-ET/ICSI后妊娠结局的影响。方法：收集2018年2月到2023年6月在中国人民解放军联勤保障部队第九四〇医院生殖医学中心行IVF-ET/ICSI的薄型子宫内膜患者204例。移植前未行特殊治疗的患者为对照组（A组，52例），行子宫内膜搔刮治疗者为搔刮组（B组，60例），行G-CSF宫腔灌注者为灌注组（C组，48例），行内膜搔刮联合宫腔灌注者为联合组（D组，44例）。比较对照组与各治疗组患者的一般资料、临床资料、移植胚胎情况、移植时子宫内膜情况以及移植后的胚胎种植率、临床妊娠率、生化妊娠率、早期流产率、多胎妊娠率、早产率以及活产率。结果：对照组与各治疗组间患者的年龄（F=1.392,P=0.246）、体质指数（F=1.969,P=0.120）、不孕年限（F=0.416,P=0.742）、不孕类型（χ²=4.693,P=0.196）、不孕因素（χ²=7.206,P=0.616）、内膜准备方法（χ²=11.289,P=0.256）、基础卵泡刺激素（follicle stimulating hormone,FSH）(F=1.736,P=0.161)、黄体生成素（luteinizing hormone,LH）(F=1.894,P=0.132)、雌二醇（estradiol,E2）(F=1.614,P=0.181)、既往移植次数（χ²=4.041,P=0.257）、妊娠次数（F=0.024,P=0.995）、流产次数（F=0.118,P=0.949）、移植胚胎个数（F=0.345,P=0.793）、移植胚胎发育天数（χ²=1.638,P=0.651）比较，差异无统计学意义。B组、C组、D组移植日子宫内膜厚度均高于A组（7.93±1.34、8.06±0.85、7.79±1.20 vs. 6.81±0.91,F=13.88,P<0.001）,B组、C组、D组移植日Ⅲ型内膜血流较A组均增高（56.7%、54.2%、56.8%vs. 28.8%，χ²=13.70,P=0.003），差异均具有统计学意义。B组、C组、D组的胚胎种植率及临床妊娠率均明显高于A组（51.1%、39.2%、48.6%vs. 22.0%，χ²=18.095,P<0.001）、（65.0%、58.3%、54.5 vs. 28.9%，χ²=16.116,P=0.001），差异有统计学意义。B组与C组的生化妊娠率明显高于A组（68.3%、66.7%vs. 40.4%，χ²=10.936,P=0.012），差异有统计学意义。D组的多胎妊娠率明显高于B组与C组（45.8%vs. 20.5%、10.7%，χ²=9.476,P=0.024），差异有统计学意义。B组、C组、D组的活产率均明显高于A组（55.0%、47.9%、47.7%vs. 19.2%，χ²=16.410,P=0.001），差异有统计学意义。A组与B组、C组、D组之间的早期流产率及早产率比较，差异均无统计学意义（P>0.05）。B组、C组、D组之间的胚胎种植率、临床妊娠率、生化妊娠率、早期流产率及早产率比较，差异均无统计学意义（P>0.05）。结论：子宫内膜搔刮、宫腔灌注G-CSF单一治疗以及两者联合治疗均能增加TE患者的子宫内膜厚度，且均能改善TE患者行IVF-ET/ICSI后的妊娠结局，但3种治疗措施间的临床疗效并无明显差异，且联合治疗较单独治疗能增加TE患者行IVF-ET/ICSI的多胎妊娠率，增加病理妊娠发生的风险。

Abstract

Objective To compare the effect of monotherapies and combination therapy of endometrial curettage and intrauterine perfusion of granulocyte colony-stimulating factor（G-CSF） on pregnancy outcomes after in vitro fertilization and embryo transfer/intracytoplasmic sperm injection（IVF-ET/ICSI） in patients with thin endometrium（TE）. Methods A total of 204 patients with TE who underwent IVF-ET/ICSI in the Reproductive Medicine Center of the 940 Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army from February 2018 to June 2023 were collected. The patients who did not receive special treatment before transplantation were included in control group（group A，52 patients），those who underwent endometrial curettage in curettage group（group B，60 patients），those who underwent intrauterine perfusion of G-CSF in perfusion group（group C，48 patients），and those who underwent endometrial curettage combined with intrauterine perfusion in combination therapy group（group D，44 patients）. The general information，clinical data，embryo transfer，endometrial condition at the time of transfer，embryo implantation rate，clinical pregnancy rate，biochemical pregnancy rate，early miscarriage rate，multiple pregnancy rate，preterm birth rate，and live birth rate were compared between the control group and the treatment groups. Results No significant difference was observed in the age（F=1.392，P=0.246），body mass index（F=1.969，P=0.120），infertility years（F=0.416，P=0.742），infertility type（χ² =4.693，P=0.196），infertility factors（χ²=7.206，P=0.616），endometrial preparation method（χ² =11.289，P=0.256），basic follicle-stimulating hormone（F=1.736，P=0.161），luteinizing hormone（F=1.894，P=0.132），estradiol（F=1.614，P=0.181），number of previous transplants（χ² =4.041，P=0.257），number of pregnancies（F=0.024，P=0.995），number of miscarriages（F=0.118，P=0.949），number of embryos transferred（F=0.345，P=0.793），and developmental days of the transferred embryos（χ² =1.638，P=0.651） between the control group and the treatment groups. The endometrial thickness and type Ⅲ endometrial blood flow of groups B，C，and D on the day of transplantation were significantly higher than those of group A （7.93±1.34，8.06±0.85，7.79±1.20 vs. 6.81±0.91，F=13.88，P<0.001； 56.7%，54.2%，56.8% vs. 28.8%，χ² =13.70，P=0.003） and so were the embryo implantation rate and clinical pregnancy rate（51.1%，39.2%，48.6% vs. 22.0%，χ² =18.095，P<0.001；65.0%，58.3%，54.5 vs. 28.9%，χ² =16.116，P=0.001）. The biochemical pregnancy rate of groups B and C was significantly higher than that of group A （68.3%，66.7% vs. 40.4%，χ² =10.936，P=0.012）. The multiple pregnancy rate of group D was significantly higher than that of groups B and C（45.8% vs. 20.5%，10.7%，χ² =9.476，P=0.024）. The live birth rate of groups B，C，and D was significantly higher than that of group A（55.0%，47.9%，47.7% vs. 19.2%，χ² =16.410，P=0.001）. There were no significant differences in the early miscarriage rate and preterm birth rate in group A compared with groups B，C，and D（P>0.05），and in the embryo implantation rate，clinical pregnancy rate，biochemical pregnancy rate，early miscarriage rate，and preterm birth rate between groups B，C and D（P>0.05）. Conclusion The monotherapies and combination therapy of endometrial curettage and intrauterine perfusion of G-CSF increase the endometrial thickness and improve the pregnancy outcome after IVF-ET/ICSI in TE patients，with no significant difference in therapeutic effect. Moreover，the combination therapy increases the multiple pregnancy rate and the risk of pathological pregnancy in TE patients with IVF-ET/ICSI compared with the monotherapy.

关键词

宫腔灌注 / 内膜搔刮 / 粒细胞集落刺激因子 / 薄型子宫内膜 / 冻融胚胎移植

Key words

intrauterine perfusion / endometrial curettage / granulocyte colony-stimulating factor / thin endometrium / frozen-thawed embryo transfer

基金资助

中央高校基本科研资助项目(31920200001)

甘肃省自然科学基金资助项目(22JR11RA010)

军队科研后勤资助项目(2023HQZZ-04)