新鲜体外受精与胚胎移植周期子代低出生体重发生风险及其相关因素分析

Risk of low birth weight infants in women conceived through in vitro fertilization and fresh embryo transfer

目的探讨新鲜体外受精与胚胎移植周期子代低出生体重发生风险及其相关因素。方法回顾性分析2011年1月至2016年12月在中山大学孙逸仙纪念医院接受常规体外受精或卵母细胞内单精子注射新鲜胚胎移植并分娩的4930例活产儿的病历资料,其中3474例为单胎、1456例为双卵双胎。根据活产儿是否为低出生体重,将3474例单胎分为低出生体重单胎组(252例)和单胎对照组(3222例);1456例双卵双胎分为低出生体重双胎组(1014例)和双胎对照组(442例),分析低出生体重组与对照组活产儿的临床特点,以及低出生体重发生的风险因素。采用两独立样本t检验、Mann-WhitneyU检验、χ^2检验及logistic回归分析进行统计学分析。结果(1)3474例单胎活产儿中,低出生体重发生率为7.25%(252/3474);1456例双卵双胎活产儿中,低出生体重发生率为69.64%(1014/1456)。(2)单胎活产儿中,低出生体重组母亲体重指数低于对照组[(20.9±2.8)与(21.3±2.7)kg/m2,t=2.162,P=0.031],但早产的发生率及移植囊胚期胚胎比例均高于对照组[分别为61.7%(153/252)与5.7%(182/3222),8.7%(22/252)与5.1%(163/3222),χ^2值分别为814.232和6.234,P值均<0.05]。(3)双卵双胎活产儿中,低出生体重组母亲年龄、父亲年龄、早产的发生率及扳机日雌二醇水平[M(P25~P75)]均大于对照组[分别为(31.0±3.7)与(30.5±3.9)岁,(33.7±5.0)与(32.7±4.5)岁,63.0%(631/1014)与28.0%(123/442),11362.3(7549.2~16716.1)与10444.8(7079.4~14569.9)pmol/L,t、χ^2或Z值分别为-2.498、-3.680、150.295及-2.570,P值均<0.05]。(4)经多因素回归分析,单胎活产儿中,早产、母亲体重指数<18.5kg/m2、女性胎儿为低出生体重发生的独立危险因素(校正后OR值分别为28.45、1.59及1.45,95%CI分别为20.87~38.80、1.06~2.41及1.06~1.97,P值均<0.05);双卵双胎活产儿中,早产、扳机日雌二醇水平过高(>10970pmol/L)、双胎性别不同为低出生体重发生的独立危险因素(校正后OR值分别为4.51、1.35及1.45,95%CI分别为3.50~5.82、1.06~1.74及1.09~1.93,P值均<0.05)。结论卵巢刺激后的高雌激素水平可能是新鲜体外受精与胚胎移植周期分娩双卵双胎新生儿低出生体重增加的危险因素。

Objective To analyze the risk factors of low birth weight (LBW) in infants who were conceived through fresh embryo transfer after in vitro fertilization. Methods We retrospectively reviewed the medical records of 4 930 live babies born after in vitro fertilization/intra-cytoplasmic sperm injection- embryo transfer (IVF/ICSI-ET) at Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University between January 2011 to December 2016. They were 3 474 singletons and 1 456 pairs of dizygotic twins. According to their birth weight, all singletons were divided into two groups: the LBW singleton group (<2 500 g, n=252) and the control singleton group (≥2 500 g, n=3 222). Two dizygotic twin groups, the LBW dizygotic twin group (<2 500 g, n=1 014) and the control dizygotic twin group (≥2 500 g, n=442), were set up as well. Clinical characteristics of the infants in different groups and risk factors of LBW were analyzed. Independent samples t-test, Mann-Whitney U test, Chi-square test, and logistic regression were used for statistical analysis. Results (1) The rates of LBW were 7.25%(252/3 474) in singletons and 69.64%(1 014/1 456) in dizygotic twins.(2) In singleton pregnancies, the maternal body mass index (BMI) of the LBW group was lower than that of the control group [(20.9±2.8) vs (21.3±2.7) kg/m2, t=2.162, P=0.031], while the rates of preterm delivery and blastocyst transfer were higher [61.7%(153/252) vs 5.7%(182/3 222), 8.7%(22/252) vs 5.1%(163/3 222),χ^2=814.232 and 6.234, respectively, all P<0.05].(3) In dizygotic twin pregnancies, maternal age, paternal age, the rate of preterm delivery and estradiol (E2) level [M(P25-P75)] at trigger were higher than those of the control group [(31.0±3.7) vs (30.5±3.9) years,(33.7±5.0) vs (32.7±4.5) years, 63.0%(631/1 014) vs 28.0%(123/442), 11 362.3 (7 549.2-16 716.1) vs 10 444.8(7 079.4-14 569.9) pmol/L;the values of t or χ^2 or Z were -2.498,-3.680, 150.295 and -2.570, all P<0.05].(4) Multivariate logistic regression analysis revealed that preterm delivery, maternal BMI<18.5 kg/m2 and girl baby were independent risk factors for LBW in singleton pregnancies (adjusted OR=28.45, 1.59 and 1.45, 95%CI: 20.87-38.80, 1.06-2.41 and 1.06-1.97, all P<0.05). Preterm delivery, high E2 level at trigger (>10 970 pmol/L) and different gender of twins were independent risk factors for LBW in dizygotic twin pregnancies (adjusted OR=4.51, 1.35 and 1.45, 95%CI: 3.50-5.82, 1.06-1.74 and 1.09-1.93, all P<0.05). Conclusions High maternal serum E2 level after controlled ovarian stimulation (COS) in fresh embryo transfer cycle may be one of the risk factors for LBW in twin pregnancies.