卵泡液褪黑素水平与单周期体外受精-胚胎移植女性妊娠率的关联强度

Strength of association between follicular fluid melatonin levels and pregnancy rates in single-cycle in vitro fertilization-embryo transfer women

背景:体外受精-胚胎移植常用来解决不孕症,但其成功率不高,较为常见的原因有子宫内膜容受能力差、卵子质量差等,卵泡液褪黑素能抑制卵巢衰老,一定程度上可促进胚胎发育,提高受孕概率,但二者之间是否存在关联尚不可知。目的:探究卵泡液褪黑素水平与单周期体外受精-胚胎移植女性妊娠率的相关性。方法:选取2020年12月至2021年4月在安徽医科大学第一附属医院接受体外受精-胚胎移植治疗的112例女性患者为研究对象,按照卵泡液褪黑素水平从低到高分为五分位数组(Q1-Q5),其中Q1组褪黑素水平<6.99 ng/L(n=18)、Q2组褪黑素水平7.00-9.99 ng/L(n=26)、Q3组褪黑素水平10.00-11.99 ng/L(n=27)、Q4组褪黑素水平12.00-13.99 ng/L(n=18)、Q5组褪黑素水平14.00-19.99 ng/L(n=23),比较5组患者的临床资料特征。采用多因素Logistic回归分析卵泡液褪黑素水平与单周期体外受精-胚胎移植女性妊娠率的相关性,建立限制性立方样条Logistic回归模型分析其剂量-反应关系,并通过临床决策曲线进行模型评价。结果与结论:①与最低褪黑素五分位数(Q1)的研究人群相比,随着褪黑素水平升高(Q2-Q5),获卵数、妊娠成功构成比水平逐渐增高,体质量指数逐渐降低,差异有显著性意义(P<0.05);②多因素Logistic回归分析显示,调整体质量指数、获卵数、促黄体生成素、雌二醇、孕酮等混杂因素后,卵泡液褪黑素水平仍与单周期体外受精-胚胎移植女性妊娠率存在独立相关性(OR=1.538,95%CI:1.032-1.837,P<0.05),且卵泡液褪黑素水平从低到高五分位数组趋势性检验差异有显著性意义(P_(趋势)<0.05);③敏感性检验分析显示E值为2.117,亚组分析显示卵泡液促黄体生成素水平较高的研究人群,其卵泡液褪黑素与单周期体外受精-胚胎移植女性妊娠率相关性更明显(P_(交互)=0.008);④限制性立方样条模型分析结果显示,卵泡液褪黑素水平与单周期体外受精-胚胎移植女性妊娠率的关联强度呈非线性剂量反应关系(P<0.05),卵泡液褪黑素水平与单周期体外受精-胚胎移植女性妊娠率呈显著正相关;⑤临床决策曲线分析结果显示,卵泡液褪黑素水平对预测单周期体外受精-胚胎移植女性妊娠率具有重要的临床价值;⑥结果表明,卵泡液褪黑素水平与单周期体外受精-胚胎移植女性妊娠率密切相关,且随着卵泡液褪黑素水平降低,单周期体外受精-胚胎移植女性妊娠率随之下降。

BACKGROUND:In vitro fertilization-embryo transfer is commonly used to solve infertility,but its success rate is not high,the more common reasons are poor endometrial receptivity,poor egg quality,etc.The follicular fluid melatonin can inhibit the aging of the ovary,to a certain extent,can promote the development of embryos,improve the probability of conception,but whether there is a correlation between the two is not known.OBJECTIVE:To explore the correlation between follicular fluid melatonin level and pregnancy rate of single-cycle in vitro fertilization-embryo transfer women.METHODS:A total of 112 female patients who received in vitro fertilization-embryo transfer treatment in the First Affiliated Hospital of Anhui Medical University from December 2020 to April 2021 were selected as the study subjects.They were divided into quartile array(Q1-Q5)according to the follicular fluid melatonin level from low to high.Among them,the melatonin level of group Q1 was<6.99 ng/L(n=18),that of group Q2 was 7.00-9.99 ng/L(n=26),that of group Q3 was 10.00-11.99 ng/L(n=27),and that of group Q4 was 12.00-13.99 ng/L(n=18);and melatonin levels in group Q5 were 14.00-19.99 ng/L(n=23).Clinical data characteristics of the five groups were compared.Multi-factor Logistic regression was used to analyze the correlation between follicular fluid melatonin level and pregnancy rate of women with single-cycle in vitro fertilization-embryo transfer and embryo transfer.A restricted cubic spline Logistic regression model was established to analyze the dose-response relationship,and the model was evaluated by clinical decision curve.RESULTS AND CONCLUSION:(1)Compared with the study population with the lowest melatonin quintile(Q1),with the increase of melatonin level(Q2-Q5),the levels of egg harvest and pregnancy success were gradually increased,and the body mass index was gradually decreased,and the differences were significant(P<0.05).(2)Multivariate Logistic regression analysis showed that after adjusting for confounding factors such as global mass index,number of eggs retrieved,luteinizing hormone,estradiol,progesterone and other confounding factors,follicular fluid melatonin level was still independently correlated with pregnancy rate of single-cycle in vitro fertilization-embryo transfer women(OR=1.538,95%CI:1.032-1.837,P<0.05),and there was significant difference in trend test of follicular fluid melatonin level from low to high quintile array(P_(trend)<0.05).(3)The sensitivity test analysis showed that E value was 2.117.Subgroup analysis showed that the study population with higher levels of luteinizing hormone in follicular fluid had a more significant association between follicular fluid melatonin and pregnancy rate in single-cycle in vitro fertilization-embryo transfer women(P_(interaction)=0.008).(4)The results of restricted cubic spline model analysis showed that there was a nonlinear dose-response relationship between follicular fluid melatonin level and pregnancy rate of single-cycle in vitro fertilization-embryo transfer women(P<0.05),and there was an overall positive correlation between follicular fluid melatonin level and pregnancy rate of single-cycle in vitro fertilization-embryo transfer women.(5)The results of clinical decision curve analysis showed that the follicular fluid melatonin level had important clinical value in predicting the pregnancy rate of single-cycle in vitro fertilization-embryo transfer women.(6)Follicular fluid melatonin level is closely related to the pregnancy rate of single-cycle in vitro fertilization-embryo transfer women,and with the decrease of follicular fluid melatonin level,the pregnancy rate of single-cycle in vitro fertilization-embryo transfer women also decreases.