宫腔微生物与辅助生殖妊娠结局的相关性分析

Correlation analysis of intrauterine microflora and pregnancy outcomes of assisted reproduction

目的了解不孕女性宫腔微生态状况,探索宫腔微生物与妊娠结局的关系。方法选取2019年10~12月在我院生殖医学中心行体外受精/卵胞浆内单精子注射(IVF/ICSI)助孕并接受冻融胚胎移植(FET)的不孕患者为研究对象,共238个周期,患者胚胎移植操作后,对其胚胎移植导管的内管尖端进行细菌培养,利用基质辅助激光解析串联飞行时间质谱(MALDI-TOF)对培养菌落进行鉴定,根据鉴定结果并按宫腔内细菌检测是否以乳杆菌为主要菌群分为3组,只含乳杆菌的为乳杆菌主导组(n=122)、未培养出任何细菌的为检测阴性组(n=40)、同时含乳杆菌与非乳杆菌的为非乳杆菌组(n=76)。比较3组患者的一般资料,结合其临床资料分析宫腔微生物与妊娠结局的关系。结果MALDI-TOF鉴定结果表明,宫腔内检出细菌的移植周期占83.19%(198/238)。3组患者的年龄、配偶年龄、体重指数(BMI)、不孕年限、不孕类型、不孕因素、基础FSH、子宫内膜厚度、移植胚胎类型、移植胚胎个数及周期内膜准备方案比较均无显著性差异(P>0.05);乳杆菌主导组和非乳杆菌组中的抗苗勒管激素(AMH)均显著低于检测阴性组(P<0.05);3组患者临床妊娠率分别为78.69%、65.00%和36.84%,乳杆菌主导组临床妊娠率显著高于非乳杆菌组(P<0.05)。Logistic分析显示,当宫腔内菌群为非乳杆菌时可以使临床妊娠率显著降低84%[OR=0.16,95%CI(0.06,0.39),P<0.05],调整潜在混杂因素后,宫内菌群仍是影响妊娠结局的独立危险因素87%[OR=0.13,95%CI(0.04,0.38),P<0.01]。结论接受辅助生殖助孕的不孕女性宫腔内乳杆菌为优势菌群,宫腔内的非乳杆菌菌群是影响辅助生殖结局的独立危险因素,宫腔内异常菌群的存在可能影响妊娠结局。

Objective:To understand the status of intrauterine microflora in infertile women and the relationship between uterine microecology and the pregnancy outcomes of assisted reproduction.Methods:The data of 238 frozen embryo transfer(FET)cycles of infertility patients with IVF/ICSI treatment in our center from October 2019 to December 2019 was selected to analyze.After the patient’s embryo transfer operation,bacterial culture was performed on the tip of the inner tube of the embryo transfer catheter.The cultured colonies were identified by using matrix-assisted laser analysis tandem time-of-flight mass spectrometry(MALDI-TOF).According to the identification results and whether lactobacillus was the main bacterial group in the intrauterine bacterial test,the cycles were divided into 3 groups:those containing only lactobacillus was the lactobacillus dominant group(n=122),and those that did not cultivated any bacteria was the negative group(n=40),those containing both lactobacillus and non-lactobacillus was the non-lactobacillus dominated group(n=76).The general data of the patients of three groups were compared,and the relationship between the intrauterine microflora and pregnancy outcome was analyzed in combination with their clinical data.Results:The MALDI-TOF identification results showed that the transplantation cycle of bacteria detected in the uterine cavity accounted for 83.19%(198/238).There were no significant differences in woman’s age,spouse age,BMI,duration and type of infertility,infertile causes,basic FSH,endometrial thickness,type and number of embryos transferred,and endometria preparation protocol among the three groups(P>0.05).The anti-Müllerian hormone(AMH)in the lactobacillus dominated group and the non-lactobacillus dominated group was significantly lower than that in the negative group(P<0.05).The clinical pregnancy rates were 78.69%,65.00%and 36.84%among the three groups.The clinical pregnancy rate of lactobacillus dominated group was significantly higher than that of non-lactobacillus dominated group(P<0.05).Multivariate analysis showed when the intrauterine flora was non-lactobacillus,the clinical pregnancy rate was significantly reduced by 84%[OR=0.16,95%CI(0.06,0.39),P<0.05].After adjusting for relevant risk factors,the correlation results were not significantly changed[OR=0.13,95%CI(0.04,0.38),P<0.01].Conclusions:The uterine flora of infertile women receiving assisted reproduction therapy is mainly lactobacillus.The non-lactobacillus flora in the uterine cavity is an independent risk factor affecting the outcome of assisted reproduction.The presence of abnormal flora in the uterine cavity may affect the outcome of pregnancy.