卵泡输出率对不孕患者卵巢反应性及妊娠结局的预测价值

Value of follicular output rate in predicting ovarian response and pregnancy outcome of infertile patients

目的探讨在体外受精-胚胎移植(IVF-ET)中,卵泡输出率(FORT)对不孕患者卵巢反应性及临床妊娠率的预测价值。方法选择2010年1月1日至2014年12月31日,在武汉大学中南医院生殖医学中心进行IVF-ET治疗的768例不孕患者为研究对象。本研究中,FORT为注射人绒毛膜促性腺激素(hCG)当日,直径为14～22mm排卵前卵泡数(PFC)与直径为3～8mm窦卵泡计数(AFC)的比值。根据其FORT值,将其分为低FORT值组(n=255,FORT值小于所有受试者FORT值的第33位百分位数,即FORT值<0.36),中FORT值组(n=277,FORT值处于所有受试者FORT值的第33～67位百分位数,即FORT值为0.36～0.67),高FORT值组(n=236,FORT值大于所有受试者FORT值的第67位百分位数,即FORT值>0.67)。采用回顾性分析方法,采集3组患者的一般临床资料及控制性促排卵相关指标。采用单因素方差分析,对于3组患者的年龄、人体质量指数(BMI)、基础卵泡刺激素(FSH)、AFC、促性腺激素(Gn)总量、Gn使用时间、注射hCG当日雌二醇水平、PFC、获卵数、MⅡ卵子数、移植胚胎数等进行比较。采用最小显著差异法(LSD)法,对3组患者AFC进一步进行两两比较。采用Kruskal-Wallis H秩和检验,对3组患者不孕年限、基础促黄体激素(LH)、基础雌二醇水平等进行比较。采用χ~2检验,对3组患者不孕原因构成比、优质胚胎率、胚胎种植率、临床妊娠率、活产率等进行比较。采用Pearson相关性分析,对不孕患者FORT与其获卵数、可利用胚胎数、优质胚胎数、年龄、基础FSH水平、基础雌二醇水平的相关性进行分析。对于不孕患者临床妊娠率的影响因素,进行多因素非条件logistic回归分析。本研究遵循的程序符合武汉大学中南医院伦理委员会所制定的伦理学标准,得到该委员会批准(审批文号:2017109)。结果 (1)3组患者的年龄、BMI、不孕年限、不孕原因构成比等一般临床资料比较,差异均无统计学意义(P>0.05)。(2)3组患者的基础FSH、基础LH、基础雌二醇水平分别整体比较,差异均无统计学意义(P>0.05)。低、中、高FORT值组患者的AFC分别为(15.2±3.2)个、(14.3±3.7)个和(13.8±3.5)个,3组比较,差异有统计学意义(F=56.547,P<0.001)。(3)3组患者注射hCG当日雌二醇水平、PFC、获卵数、MⅡ卵子数、可利用胚胎数、双原核受精率、优质胚胎率、胚胎种植率、临床妊娠率和活产率比较,差异均有统计学意义(F=64.974、215.869、26.344、22.904,H=59.625,χ~2=32.985、16.532、21.324、14.319、12.644,均为P<0.001)。3组患者的Gn总量、Gn使用时间、移植胚胎数比较,差异均无统计学意义(P>0.05)。(4)不孕患者中,FORT与获卵数(r=0.286,P<0.001),可利用胚胎数(r=0.327,P<0.001)及优质胚胎数(r=0.252,P<0.001)均呈正相关关系;但是,FORT与年龄(r=0.021,P=0.063)、基础FSH水平(r=-0.019,P=0.169)及基础雌二醇(r=0.023,P=0.088)之间无相关性。(5)对不孕患者临床妊娠率影响因素进行多因素非条件logistic回归分析的结果显示,FORT是不孕患者临床妊娠率的独立影响因素(OR=1.023,95%CI:1.003～1.043,P=0.027)。结论 FORT可作为不孕患者卵巢窦卵泡对FSH的反应性、妊娠结局的有效预测指标。但是,因为本研究仅为回顾性研究,FORT对不孕患者卵巢反应性及妊娠结局的预测价值,仍有待大样本、多中心、前瞻性研究进一步证实。

Objective To investigate clinical values of follicular output rate(FORT)in predicting ovarian response and pregnancy outcome of infertile patients with in vitro fertilization and embryo transfer(IVF-ET).Methods From January 1,2010 to December 31,2014,a total of 768 infertile patients who were treated with IVF-ET in Reproductive Medicine Center of Zhongnan Hospital of Wuhan University were collected as research subjects.In this study,FORT was the ratio of the number of preovulatory follicles(PFC)with a diameter of 3 to 8 mm and the antral follicle count(AFC)of 14 to 22 mm on the day of human chorionic gonadotropin(hCG)injection.According to FORT value,they were divided into 3 groups,low FORT value group(n=255,FORT value was lower than the 33rd percentile of the FORT value of all subjects,i.e.FORT value<0.36),middle FORT value group(n=277,FORT value was in the 33th to 67th percentile of the FORT value of all subjects,i.e.FORT value was 0.36 to 0.67),and high FORT value group(n=236,FORT value was higher than the 67th percentile of the FORT value of all subjects,i.e.FORT value>0.67).The general clinical data and related indicators of controlled ovulation hyperstimulation of 3 groups were collected by retrospective analysis.The age,body mass index(BMI),basal follicle stimulating hormone(FSH),AFC,total amount of gonadotropin(Gn),Gn use days,estradiol level on the day of hCG injection,PFC,number of ovums obtained,number of MⅡovums and number of embryos transferred were analyzed by one-way ANOVA analysis.The least significant difference(LSD)method was used to analyze AFC among three groups in further pairwise comparison.The duration of infertility,basic luteinizing hormone(LH)and basal estradiol levels were analyzed by Kruskal-Wallis H rank sum test.Chi-square test was used to analyze the ratio of different causes of infertility,high-quality embryos rate,embryo implantation rate,clinical pregnancy rate and live birth rate.Pearson correlation analysis was used to analyze the correlation between FORT and number of ovums obtained,number of available embryos,number of high quality embryos,age,basal FSH level and basal estradiol level,respectively.Influencing factors of clinical pregnancy rate in infertile patients were analyzed by multivariate unconditional logistic regression analysis.The procedures followed in this study were approved by the Ethics Committee of Zhongnan Hospital of Wuhan University(Approval Number:2017109).Results①There were no significant differences among three groups in age,BMI,infertile duration,ratio of causes of infertility and other general clinical data(P>0.05).②There were no significant differences in basal FSH,basal LH and basal estradiol levels among three groups(P>0.05).The number of AFC of low,middle and high FORT value group groups were 15.2±3.2,14.3±3.7 and 13.8±3.5,respectively,and the difference was statistically significant(F=56.547,P<0.001).③There were significant differences in estradiol level on the day of hCG injection,PFC,number of ovums obtained,number of MⅡovums,number of available embryos,double pronucleus fertilization rate,high quality embryo rate,embryo implantation rate,clinical pregnancy rate and live birth rate among three groups(F=64.974,215.869,26.344,22.904,H=59.625,χ2=32.985,16.532,21.324,14.319,12.644;all P<0.001).However,there were no significant differences in total amount of Gn,Gn use days,and number of embryos transferred among three groups(P>0.05).④Among all the infertile patients in this study,FORT had positive correlation with the number of ovums obtained(r=0.286,P<0.001),number of available embryos(r=0.327,P<0.001)and number of high quality embryos(r=0.252,P<0.001),but FORT had no correlation with age(r=0.021,P=0.063),basal FSH level(r=-0.019,P=0.169),basal estradiol level(r=0.023,P=0.088).⑤The results of multivariate unconditional logistic regression analysis on influencing factors of clinical pregnancy rate of infertile patients showed that FORT was the independent influencing factor on the clinical pregnancy rate of infertile patients(OR=1.023,95%CI:1.003-1.043,P=0.027).Conclusions FORT can be used as an effective index to predict ovarian antral follicles′response to FSH and pregnancy outcome of infertile patients.However,because this study is just a retrospective study,the value of FORT in predicting ovarian response and pregnancy outcome in infertile patients remains to be confirmed by large,multicenter,prospective studies.