人类辅助生殖技术助孕的母儿围产结局研究

发布时间：2018-09-06 15:59

【摘要】：研究目的:1978年世界首例试管婴儿诞生以来,辅助生殖技术已逐渐成为治疗不孕不育夫妇的重要手段。该技术主要包括体外受精-胚胎移植(IVF-ET),卵细胞浆内单精子注射(ICSI),冻融复苏胚胎移植(FET)以及胚胎植入前遗传学筛查及诊断(PGS/PGD)。然而,辅助生殖技术与自然妊娠不同,它涉及一系列非生理的过程:超促排卵、手术取卵、体外受精、显微注射以及胚胎移植等,还可能发生包括卵巢过度刺激综合征(OHSS)、多胎妊娠(MP)等一系列的并发症,因此,IVF术后母儿的安全性受到了高度的关注。目前,国内外对这一结局的报道均不一致。基于此,本研究回顾了我中心患者的围产期状况与新生儿出生情况,拟为这尚存争议的问题提供更多的理论数据依据及参考。第一部分人类辅助生殖技术助孕的母亲围产期并发症方法:选取2011年1月至2014年7月西南医院生殖中心行IVF助孕技术并成功活产的孕妇1237例(助孕组),其中新鲜胚胎移植周期(fresh embryo transfer)711例(鲜胚组),冻融复苏胚胎移植周期(frozen thawed embryo transfer)526例(冻胚组),并以2014年我院产科收治的自然妊娠孕妇5040例作为对照(对照组)。排除标准为:助孕组排除冻卵周期、赠卵周期以及失访的患者。所有病例均通过病历回顾及电话随访等途径了解两组母亲围产期并发症情况,所有数据均得到患者及其家属的知情同意且通过第三军医大学伦理委员会的审批[2015年科研第(67)号]。收集以下数据:1、基本情况:助孕组不孕原因、患者年龄;2、助孕组复杂性妊娠:流产率、异位妊娠率;3、围产期并发症:妊娠期高血压(pregnancy-induced hypertension,PIH)、子痫前期、前置胎盘(placenta previa)、胎盘早剥(placental abruption)、胎膜早破(premature rupture of fetal membranes,PROM)、妊娠期肝内胆汁淤积症(intrahepaticcholestasis in pregnancy,ICP)和产后出血(postpartum hemorrhage);4、生产经过:生产方式(阴道分娩/剖宫产)、入ICU率。结果:1、助孕组平均年龄为30.4±4.2岁,不孕原因构成中,盆腔及输卵管因素962例(77.8%),排卵障碍35例(2.8%),子宫内膜异位症26例(2.1%),其余为原因不明和男方因素(无精症、极度少弱精症等);对照组平均年龄为29.0±4.0岁,两组差异显著(P0.05)。2、助孕组内鲜胚平均年龄为30.6±4.3,冻胚平均年龄为30.2±4.2,两组无差异;鲜胚的早期流产117例,晚期流产60例,异位妊娠34例;冻胚的早期流产115例,晚期流产18例,异位妊娠33例,鲜胚早期流产率较低,晚期流产率较高(P0.05),异位妊娠率无差异(P0.05)。3、助孕组围产期并发症总发生率为(53%,656/1237),其中PIH104例,子痫前期13例,前置胎盘145例,胎盘早剥7例,PROM257例,ICP74例,产后出血56例;对照组围产期并发症总发生率为(33.1%,1667/5040),其中PIH56例,子痫前期50例,前置胎盘176例,胎盘早剥24例,PROM1057例,ICP219例,产后出血85例。与对照组比较,助孕组PIH、前置胎盘、ICP以及产后出血的发生率较高(P0.05)。4、助孕组内鲜胚组围产期并发症总发生率为(42.8%,304/711),其中PIH58例,子痫前期8例,前置胎盘74例,胎盘早剥4例,PROM109例,ICP27例,产后出血24例;冻胚组围产期并发症总发生率为(66.9%,352/526),其中PIH46例,子痫前期5例,前置胎盘71例,胎盘早剥3例,PROM148例,ICP47例,产后出血32例。与鲜胚组比较,冻胚组ICP、PROM以及产后出血的发生率较高(P0.05)。5、单胎妊娠,助孕组围产期并发症总发生率为(51.3%,457/891),其中PIH66例,子痫前期11例,前置胎盘112例,胎盘早剥5例,PROM172例,ICP58例,产后出血33例;对照组围产期并发症总发生率为(32.8%,1620/4944),其中PIH52例,子痫前期46例,前置胎盘172例,胎盘早剥21例,PROM1038例,ICP209例,产后出血82例。与对照组比较,助孕组PIH、前置胎盘、ICP以及产后出血的发生率高(P0.05)。6、双胎妊娠,助孕组围产期并发症总发生率为(57.5%,199/346),其中PIH38例,子痫前期2例,前置胎盘33例,胎盘早剥2例,PROM85例,ICP16例,产后出血23例;对照组围产期并发症总发生率为(49%,47/96),其中PIH4例,子痫前期4例,前置胎盘4例,胎盘早剥3例,PROM19例,ICP10例,产后出血3例。与对照组比较,助孕组ICP以及子痫前期的发生率高(P0.05)。7、助孕组孕妇剖宫产率[1127/1237(91.1%)]明显高于对照组[2450/5040(48.6%)](P0.05)。8、助孕组孕妇因孕期并发症入住ICU率也较对照组高(P0.05,10/1237 vs 3/5040),但助孕组内鲜胚组与冻胚组母亲入ICU率无差异(P0.05,4/711 vs 6/526)。结论:1、助孕组患者多有不孕的特殊疾病且平均年龄较大,其围产期PIH、前置胎盘、ICP、产后出血以及子痫前期并发症的发生率较高。2、助孕组内鲜胚组的早期流产率较低,晚期流产率较高,围产期ICP、PROM以及产后出血并发症的发生率较低。3、助孕组母亲的剖宫产率较高,因产时并发症入ICU率较高。第二部分人类辅助生殖技术助孕的子代出生结局方法:选取2011年1月至2014年7月西南医院生殖医学中心行IVF助孕技术并成功妊娠的孕妇1237例,子代共计1583例(助孕组),其中新鲜胚胎移植后出生子代925例(鲜胚组),冻融复苏胚胎移植后出生子代658例(冻胚组),并以2014年我院产科收治的自然妊娠孕妇后代5136例作为对照(对照组),随访新生儿出生时刻的情况。排除标准同第一部分。收集以下数据:1、基本情况:子代数、多胎率以及出生孕周;2、新生儿出生结局:体重、低体重儿、早产、新生儿入ICU(neonatal intensive care unit,NICU)、新生儿住院、死胎、死产及新生儿死亡;3、新生儿出生缺陷:心脏发育异常、六指畸形、尿道下裂、单脐动脉等。结果:1、助孕组后代数共计1583例,平均孕周为38.1±2.2W,其中单胎891例,双胎346例(后代692例),多胎的发生率为28%;对照组后代数共计5136例,平均孕周为38.8±1.9W,其中单胎4944例,双胎96例(后代192例),多胎的发生率为1.9%。与对照组比较,助孕组多胎率较高,后代平均出生孕周较小(P0.05)。2、助孕组内鲜胚组后代数共计925例,平均孕周为37.4±2.2W,其中单胎497例,双胎214例(后代428例),多胎的发生率为30.1%;助孕组内冻胚组后代数共计658例,平均孕周为37.9±1.9W,其中单胎394例,双胎132例(后代264例),多胎的发生率为25.1%。与冻胚组比较,鲜胚组的孕周较小(P0.05)。3、助孕组死胎、死产及新生儿死亡共计43例,NICU3例,低体重儿401例,早产150例,新生儿住院285例,后代出生平均体重2964±635(g);对照组死胎、死产及新生儿死亡共计143例,NICU0例,低体重儿346例,早产320例,新生儿住院661例,后代出生平均体重3241±531(g)。与对照组比较,助孕组NICU、低体重儿、早产以及新生儿住院的概率较高,后代体重较低(P0.05)。4、助孕组内鲜胚组死胎、死产及新生儿死亡共计25例,NICU0例,低体重儿253例,早产93例,新生儿住院162例,后代出生平均体重2900±621(g);助孕组内冻胚组死胎、死产及新生儿死亡共计18例,NICU3例,低体重儿148例,早产57例,新生儿住院123例,后代出生平均体重3055±645(g)。与冻胚组比较,鲜胚组低体重儿率较高,后代体重较低(P0.05)。5、单胎子代,助孕组NICU2例,低体重儿59例,早产63例,新生儿住院171例,后代出生平均体重3326±513(g),孕周38.7±1.8W;对照组NICU0例,低体重儿229例,早产298例,新生儿住院602例,后代出生平均体重3280±488(g),孕周38.9±1.8W。与对照组比较,助孕组NICU、低体重儿以及新生儿住院率较高,后代体重较高,孕周较小(P0.05)。6、双胎子代,助孕组NICU1例,低体重儿342例,早产87例,新生儿住院114例,后代出生平均体重2501±450(g),孕周36.4±2.2W;对照组NICU0例,低体重儿117例,早产22例,新生儿住院59例,后代出生平均体重2233±601(g),孕周35.1±3.0W。与对照组比较,助孕组低体重儿以及新生儿住院率较低,后代体重较高,孕周较大(P0.05)。7、助孕组出生缺陷发生率为1.6%,其中有13例心脏发育异常,7例六指畸形,4例尿道下裂,2例单脐动脉;对照组出生缺陷发生率1.5%,其中有10例尿道下裂,12例唇腭裂,5例单脐动脉,17例六指畸形,25例心脏发育异常,2例脐膨出,3例双肾畸形,2例外生殖器畸形,2例消化道畸形,两者新生儿出生缺陷率无差异(p0.05)。助孕组内鲜胚组(16例)与冻胚组(10例)新生儿出生缺陷率也无差异(p0.05)。结论:1、助孕组多胎率较高,孕周较小,新生儿出生体重较低。2、单胎比较,助孕组NICU、低体重儿以及新生儿住院的概率较高。3、双胎比较,助孕组低体重儿以及新生儿住院率较低,后代平均体重较高。4、助孕组内鲜胚组低体重儿率较高,平均出生体重较低。5、助孕组与对照组新生儿出生缺陷无差异。
[Abstract]:Objectives: Since the birth of the world's first test-tube baby in 1978, assisted reproductive technology (ART) has gradually become an important treatment for infertile couples. It includes in vitro fertilization-embryo transfer (IVF-ET), intracytoplasmic sperm injection (ICSI), freeze-thaw resuscitation embryo transfer (FET) and preimplantation genetic screening and diagnosis (PG). S/PGD. However, assisted reproductive technology, unlike natural pregnancy, involves a series of non-physiological processes: hyperstimulation, surgical ovulation, in vitro fertilization, microinjection, and embryo transfer. It may also produce a series of complications, including ovarian hyperstimulation syndrome (OHSS), multiple pregnancy (MP), and so on. Therefore, the safe fertilization of mothers and infants after IVF. Based on this, this study reviews the perinatal status of patients in our center and the birth of newborns, in order to provide more theoretical data and reference for the controversial issues. Part I: The perinatal period of mothers assisted by human assisted reproductive technology Methods: From January 2011 to July 2014, 1237 pregnant women (assisted pregnancy group) who underwent IVF in the reproductive center of Southwest Hospital were selected, including 711 fresh embryo transfer (fresh embryo transfer), 526 frozen thawed embryo transfer (frozen embryo transfer), and they were given live birth in our hospital in 2014. 5040 pregnant women with natural pregnancies admitted to obstetrics department were taken as control group. The exclusion criteria were: excluding frozen egg cycle, egg donation cycle and missing patients. All cases were followed up by medical records and telephone to find out the perinatal complications of the two groups. All data were informed and agreed by the patients and their families. The following data were collected through the examination and approval of the Third Military Medical University Ethics Committee [Scientific Research No. 67, 2015]: 1, basic information: infertility causes, patient age; 2, complicated pregnancy: abortion rate, ectopic pregnancy rate; 3, perinatal complications: pregnancy-induced hypertension (PIH), preeclampsia, placenta previa (p) Lacenta previa, placental abruption, premature rupture of fetal membranes (PROM), intrahepatic cholestasis in pregnancy (ICP) and postpartum hemorrhage; 4, course of labor: mode of production (vaginal delivery / cesarean section), into the ICU rate. The average age was 30.4 (+ 4.2 years). Among the causes of infertility, 962 cases (77.8%) were pelvic and fallopian tube factors, 35 cases (2.8%) were ovulation disorders, 26 cases (2.1%) were endometriosis, the others were unexplained causes and male factors (azoospermia, extremely oligospermia, etc.). The average age of the control group was 29.0 (+ 4.0 years), and the difference between the two groups was significant (P 0.05). The average age of frozen embryos was 30.6 (+ 4.3) and that of frozen embryos was 30.2 (+ 4.2) with no difference between the two groups; 117 cases of early abortion, 60 cases of late abortion, 34 cases of ectopic pregnancy; 115 cases of early abortion, 18 cases of late abortion, 33 cases of ectopic pregnancy, low early abortion rate of fresh embryos, high late abortion rate (P 0.05), no difference in ectopic pregnancy rate (P 0.05). The total incidence of perinatal complications was 53%, 656/1237, including 104 PIH cases, 13 pre-eclampsia cases, 145 placenta previa cases, 7 placental abruption cases, PROM 257 cases, ICP 74 cases, 56 cases of postpartum hemorrhage; the total incidence of perinatal complications was 33.1%, 1667/5040 in the control group, including 56 PIH cases, 50 pre-eclampsia cases, 176 placenta previa cases, 24 placental abruption cases, PROM 1057 cases. Compared with the control group, the incidence of PIH, placenta previa, ICP and postpartum hemorrhage was higher in the assisted pregnancy group (P 0.05). The total incidence of perinatal complications in the fresh embryo group was (42.8%, 304/711), including 58 cases of PIH, 8 cases of pre-eclampsia, 74 cases of placenta previa, 4 cases of placenta abruption, PROM109 cases, ICP27 cases, 24 cases of postpartum hemorrhage. The total incidence of perinatal complications in frozen embryo group was 66.9%, 352/526, including PIH46 cases, 5 cases of preeclampsia, 71 cases of placenta previa, 3 cases of placental abruption, PROM148 cases, 47 cases of ICP, 32 cases of postpartum hemorrhage. The total incidence of perinatal complications in the control group was 32.8%, 1620/4944, including PIH 52 cases, preeclampsia 46 cases, placenta previa 172 cases, placenta abruption 21 cases, PROM 1038 cases, ICP 209 cases, postpartum hemorrhage 82 cases. Compared with the control group, the incidence of PIH, placenta previa, ICP and postpartum hemorrhage was higher in assisted pregnancy group (P 0.05). The birth rate was 49%, 47/96, including PIH4, preeclampsia 4, placenta previa 4, placenta abruption 3, PROM19, ICP10, postpartum hemorrhage 3. Compared with the control group, the incidence of ICP and preeclampsia in assisted pregnancy group was higher (P 0.05). 7. The cesarean section rate in assisted pregnancy group [1127/1237 (91.1%) was significantly higher than that in control group [2450/5040 (48.6%) (P 0.05). Pregnant women also had a higher ICU admission rate due to pregnancy complications than the control group (P 0.05, 10/1237 vs 3/5040), but there was no difference in the ICU admission rate between the fresh embryo group and the frozen embryo group (P 0.05, 4/711 vs 6/526). The incidence of complications was higher. 2. The early abortion rate was lower in the fresh embryo group, the late abortion rate was higher, the incidence of perinatal ICP, PROM and postpartum hemorrhage complications was lower. 3. The cesarean section rate of the mothers in the assisted pregnancy group was higher, and the incidence of intrapartum complications was higher. Methods: From January 2011 to July 2014, 1237 pregnant women with successful IVF assisted pregnancy and 1583 offspring (assisted pregnancy group) were selected. Among them, 925 were born after fresh embryo transfer (fresh embryo group), 658 were born after frozen-thawed embryo transfer (frozen embryo group), and were treated in obstetrics department of our hospital in 2014. 5 136 pregnant women and their offspring of natural pregnancy were followed up as controls. The exclusion criteria were the same as those of the first part. The following data were collected: 1. Basic information: subalgebra, multiple pregnancy rate and gestational age; 2. Neonatal outcome: weight, low birth weight, premature delivery, neonatal intensive care unit (NICU), new. Results: 1. The number of offspring in the assisted pregnancy group was 1583, with an average gestational age of 38.1 (+ 2.2) 2 weeks, including 891 singletons, 346 twins (692 offspring), and the incidence of multiple births was 28%. The number of offspring in the control group was 5136. Compared with the control group, the multiple pregnancy rate in assisted pregnancy group was higher, and the average gestational age of offspring was smaller (P 0.05). The incidence of multiple pregnancies was 30.1%. The average gestational age of 658 offspring was 37.9 (+ 1.9W), including 394 singletons, 132 twins (264 offspring), and the incidence of multiple pregnancies was 25.1%. Compared with frozen embryo group, the gestational age of fresh embryo group was smaller (P 0.05). There were 150 preterm infants, 285 hospitalized newborns, and the average birth weight of offspring was 2964 There were 25 stillbirths, 0 stillbirths and neonatal deaths, 253 low birth weight infants, 93 preterm births, 162 hospitalized neonates, and the average birth weight of offspring was 2900 [621] (g); 18 stillbirths, 3 stillbirths and neonatal deaths in the cryopreserved embryo group, and 148 low birth weight infants in the assisted pregnancy group. Compared with frozen embryo group, fresh embryo group had a higher rate of low birth weight infants and a lower weight of offspring (P 0.05). NICU 0 cases, 229 low birth weight infants, 298 preterm infants, 602 neonates hospitalized. The average birth weight of offspring was 3280 (+) 488 (g), gestational age was 38.9 (+) 1.8 W. Compared with the control group, NICU, low birth weight infants and neonates in assisted pregnancy group had higher hospitalization rate, higher offspring weight, smaller gestational age (P 0.05). 6, twin offspring, NICU 1 in assisted pregnancy group, 342 low birth weight infants, 87 preterm infants, new born. 114 neonates were hospitalized, the average birth weight of offspring was 2501 (+) 450 (g) and the gestational age was 36.4 (+) 2.2W; the control group NICU0, 117 low birth weight infants, 22 premature infants, 59 neonates were hospitalized, the average birth weight of offspring was 2233 (+) 601 (g), and the gestational age was 35.1 (+) 3.0W. (P 0.05). 7. The incidence of birth defects in assisted pregnancy group was 1.6%. There were 13 cases of cardiac dysplasia, 7 cases of six-fingered malformation, 4 cases of hypospadias and 2 cases of single umbilical artery. The incidence of birth defects in the control group was 1.5%, including 10 cases of hypospadias, 12 cases of cleft lip and palate, 5 cases of single umbilical artery, 17 cases of six-fingered malformation, 25 cases of cardiac dysplasia, 2 cases of omphalocele, 3 cases of double kidney malformation. 2 cases of external genital malformations, 2 cases of digestive tract malformations, there was no difference in the rate of birth defects between the two groups (p0.05). There was no difference in the rate of birth defects between the fresh embryo group (16 cases) and the frozen embryo group (10 cases). Conclusion: 1. The assisted pregnancy group had a higher rate of multiple births, a smaller gestational age, a lower birth weight of newborns. And the probability of hospitalization of newborns is higher. 3. Compared with twins, the hospitalization rate of low birth weight infants and newborns in assisted pregnancy group is lower, the average weight of offspring is higher. 4. The low birth weight infants in assisted pregnancy group are higher, and the average birth weight is lower. 5. There is no difference in birth defects between assisted pregnancy group and control group.
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R714.8

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