【摘要】：研究目的:1978年世界首例試管嬰兒誕生以來,輔助生殖技術(shù)已逐漸成為治療不孕不育夫婦的重要手段。該技術(shù)主要包括體外受精-胚胎移植(IVF-ET),卵細(xì)胞漿內(nèi)單精子注射(ICSI),凍融復(fù)蘇胚胎移植(FET)以及胚胎植入前遺傳學(xué)篩查及診斷(PGS/PGD)。然而,輔助生殖技術(shù)與自然妊娠不同,它涉及一系列非生理的過程:超促排卵、手術(shù)取卵、體外受精、顯微注射以及胚胎移植等,還可能發(fā)生包括卵巢過度刺激綜合征(OHSS)、多胎妊娠(MP)等一系列的并發(fā)癥,因此,IVF術(shù)后母兒的安全性受到了高度的關(guān)注。目前,國內(nèi)外對這一結(jié)局的報道均不一致�；诖�,本研究回顧了我中心患者的圍產(chǎn)期狀況與新生兒出生情況,擬為這尚存爭議的問題提供更多的理論數(shù)據(jù)依據(jù)及參考。第一部分人類輔助生殖技術(shù)助孕的母親圍產(chǎn)期并發(fā)癥方法:選取2011年1月至2014年7月西南醫(yī)院生殖中心行IVF助孕技術(shù)并成功活產(chǎn)的孕婦1237例(助孕組),其中新鮮胚胎移植周期(fresh embryo transfer)711例(鮮胚組),凍融復(fù)蘇胚胎移植周期(frozen thawed embryo transfer)526例(凍胚組),并以2014年我院產(chǎn)科收治的自然妊娠孕婦5040例作為對照(對照組)。排除標(biāo)準(zhǔn)為:助孕組排除凍卵周期、贈卵周期以及失訪的患者。所有病例均通過病歷回顧及電話隨訪等途徑了解兩組母親圍產(chǎn)期并發(fā)癥情況,所有數(shù)據(jù)均得到患者及其家屬的知情同意且通過第三軍醫(yī)大學(xué)倫理委員會的審批[2015年科研第(67)號]。收集以下數(shù)據(jù):1、基本情況:助孕組不孕原因、患者年齡;2、助孕組復(fù)雜性妊娠:流產(chǎn)率、異位妊娠率;3、圍產(chǎn)期并發(fā)癥:妊娠期高血壓(pregnancy-induced hypertension,PIH)、子癇前期、前置胎盤(placenta previa)、胎盤早剝(placental abruption)、胎膜早破(premature rupture of fetal membranes,PROM)、妊娠期肝內(nèi)膽汁淤積癥(intrahepaticcholestasis in pregnancy,ICP)和產(chǎn)后出血(postpartum hemorrhage);4、生產(chǎn)經(jīng)過:生產(chǎn)方式(陰道分娩/剖宮產(chǎn))、入ICU率。結(jié)果:1、助孕組平均年齡為30.4±4.2歲,不孕原因構(gòu)成中,盆腔及輸卵管因素962例(77.8%),排卵障礙35例(2.8%),子宮內(nèi)膜異位癥26例(2.1%),其余為原因不明和男方因素(無精癥、極度少弱精癥等);對照組平均年齡為29.0±4.0歲,兩組差異顯著(P0.05)。2、助孕組內(nèi)鮮胚平均年齡為30.6±4.3,凍胚平均年齡為30.2±4.2,兩組無差異;鮮胚的早期流產(chǎn)117例,晚期流產(chǎn)60例,異位妊娠34例;凍胚的早期流產(chǎn)115例,晚期流產(chǎn)18例,異位妊娠33例,鮮胚早期流產(chǎn)率較低,晚期流產(chǎn)率較高(P0.05),異位妊娠率無差異(P0.05)。3、助孕組圍產(chǎn)期并發(fā)癥總發(fā)生率為(53%,656/1237),其中PIH104例,子癇前期13例,前置胎盤145例,胎盤早剝7例,PROM257例,ICP74例,產(chǎn)后出血56例;對照組圍產(chǎn)期并發(fā)癥總發(fā)生率為(33.1%,1667/5040),其中PIH56例,子癇前期50例,前置胎盤176例,胎盤早剝24例,PROM1057例,ICP219例,產(chǎn)后出血85例。與對照組比較,助孕組PIH、前置胎盤、ICP以及產(chǎn)后出血的發(fā)生率較高(P0.05)。4、助孕組內(nèi)鮮胚組圍產(chǎn)期并發(fā)癥總發(fā)生率為(42.8%,304/711),其中PIH58例,子癇前期8例,前置胎盤74例,胎盤早剝4例,PROM109例,ICP27例,產(chǎn)后出血24例;凍胚組圍產(chǎn)期并發(fā)癥總發(fā)生率為(66.9%,352/526),其中PIH46例,子癇前期5例,前置胎盤71例,胎盤早剝3例,PROM148例,ICP47例,產(chǎn)后出血32例。與鮮胚組比較,凍胚組ICP、PROM以及產(chǎn)后出血的發(fā)生率較高(P0.05)。5、單胎妊娠,助孕組圍產(chǎn)期并發(fā)癥總發(fā)生率為(51.3%,457/891),其中PIH66例,子癇前期11例,前置胎盤112例,胎盤早剝5例,PROM172例,ICP58例,產(chǎn)后出血33例;對照組圍產(chǎn)期并發(fā)癥總發(fā)生率為(32.8%,1620/4944),其中PIH52例,子癇前期46例,前置胎盤172例,胎盤早剝21例,PROM1038例,ICP209例,產(chǎn)后出血82例。與對照組比較,助孕組PIH、前置胎盤、ICP以及產(chǎn)后出血的發(fā)生率高(P0.05)。6、雙胎妊娠,助孕組圍產(chǎn)期并發(fā)癥總發(fā)生率為(57.5%,199/346),其中PIH38例,子癇前期2例,前置胎盤33例,胎盤早剝2例,PROM85例,ICP16例,產(chǎn)后出血23例;對照組圍產(chǎn)期并發(fā)癥總發(fā)生率為(49%,47/96),其中PIH4例,子癇前期4例,前置胎盤4例,胎盤早剝3例,PROM19例,ICP10例,產(chǎn)后出血3例。與對照組比較,助孕組ICP以及子癇前期的發(fā)生率高(P0.05)。7、助孕組孕婦剖宮產(chǎn)率[1127/1237(91.1%)]明顯高于對照組[2450/5040(48.6%)](P0.05)。8、助孕組孕婦因孕期并發(fā)癥入住ICU率也較對照組高(P0.05,10/1237 vs 3/5040),但助孕組內(nèi)鮮胚組與凍胚組母親入ICU率無差異(P0.05,4/711 vs 6/526)。結(jié)論:1、助孕組患者多有不孕的特殊疾病且平均年齡較大,其圍產(chǎn)期PIH、前置胎盤、ICP、產(chǎn)后出血以及子癇前期并發(fā)癥的發(fā)生率較高。2、助孕組內(nèi)鮮胚組的早期流產(chǎn)率較低,晚期流產(chǎn)率較高,圍產(chǎn)期ICP、PROM以及產(chǎn)后出血并發(fā)癥的發(fā)生率較低。3、助孕組母親的剖宮產(chǎn)率較高,因產(chǎn)時并發(fā)癥入ICU率較高。第二部分人類輔助生殖技術(shù)助孕的子代出生結(jié)局方法:選取2011年1月至2014年7月西南醫(yī)院生殖醫(yī)學(xué)中心行IVF助孕技術(shù)并成功妊娠的孕婦1237例,子代共計1583例(助孕組),其中新鮮胚胎移植后出生子代925例(鮮胚組),凍融復(fù)蘇胚胎移植后出生子代658例(凍胚組),并以2014年我院產(chǎn)科收治的自然妊娠孕婦后代5136例作為對照(對照組),隨訪新生兒出生時刻的情況。排除標(biāo)準(zhǔn)同第一部分。收集以下數(shù)據(jù):1、基本情況:子代數(shù)、多胎率以及出生孕周;2、新生兒出生結(jié)局:體重、低體重兒、早產(chǎn)、新生兒入ICU(neonatal intensive care unit,NICU)、新生兒住院、死胎、死產(chǎn)及新生兒死亡;3、新生兒出生缺陷:心臟發(fā)育異常、六指畸形、尿道下裂、單臍動脈等。結(jié)果:1、助孕組后代數(shù)共計1583例,平均孕周為38.1±2.2W,其中單胎891例,雙胎346例(后代692例),多胎的發(fā)生率為28%;對照組后代數(shù)共計5136例,平均孕周為38.8±1.9W,其中單胎4944例,雙胎96例(后代192例),多胎的發(fā)生率為1.9%。與對照組比較,助孕組多胎率較高,后代平均出生孕周較小(P0.05)。2、助孕組內(nèi)鮮胚組后代數(shù)共計925例,平均孕周為37.4±2.2W,其中單胎497例,雙胎214例(后代428例),多胎的發(fā)生率為30.1%;助孕組內(nèi)凍胚組后代數(shù)共計658例,平均孕周為37.9±1.9W,其中單胎394例,雙胎132例(后代264例),多胎的發(fā)生率為25.1%。與凍胚組比較,鮮胚組的孕周較小(P0.05)。3、助孕組死胎、死產(chǎn)及新生兒死亡共計43例,NICU3例,低體重兒401例,早產(chǎn)150例,新生兒住院285例,后代出生平均體重2964±635(g);對照組死胎、死產(chǎn)及新生兒死亡共計143例,NICU0例,低體重兒346例,早產(chǎn)320例,新生兒住院661例,后代出生平均體重3241±531(g)。與對照組比較,助孕組NICU、低體重兒、早產(chǎn)以及新生兒住院的概率較高,后代體重較低(P0.05)。4、助孕組內(nèi)鮮胚組死胎、死產(chǎn)及新生兒死亡共計25例,NICU0例,低體重兒253例,早產(chǎn)93例,新生兒住院162例,后代出生平均體重2900±621(g);助孕組內(nèi)凍胚組死胎、死產(chǎn)及新生兒死亡共計18例,NICU3例,低體重兒148例,早產(chǎn)57例,新生兒住院123例,后代出生平均體重3055±645(g)。與凍胚組比較,鮮胚組低體重兒率較高,后代體重較低(P0.05)。5、單胎子代,助孕組NICU2例,低體重兒59例,早產(chǎn)63例,新生兒住院171例,后代出生平均體重3326±513(g),孕周38.7±1.8W;對照組NICU0例,低體重兒229例,早產(chǎn)298例,新生兒住院602例,后代出生平均體重3280±488(g),孕周38.9±1.8W。與對照組比較,助孕組NICU、低體重兒以及新生兒住院率較高,后代體重較高,孕周較小(P0.05)。6、雙胎子代,助孕組NICU1例,低體重兒342例,早產(chǎn)87例,新生兒住院114例,后代出生平均體重2501±450(g),孕周36.4±2.2W;對照組NICU0例,低體重兒117例,早產(chǎn)22例,新生兒住院59例,后代出生平均體重2233±601(g),孕周35.1±3.0W。與對照組比較,助孕組低體重兒以及新生兒住院率較低,后代體重較高,孕周較大(P0.05)。7、助孕組出生缺陷發(fā)生率為1.6%,其中有13例心臟發(fā)育異常,7例六指畸形,4例尿道下裂,2例單臍動脈;對照組出生缺陷發(fā)生率1.5%,其中有10例尿道下裂,12例唇腭裂,5例單臍動脈,17例六指畸形,25例心臟發(fā)育異常,2例臍膨出,3例雙腎畸形,2例外生殖器畸形,2例消化道畸形,兩者新生兒出生缺陷率無差異(p0.05)。助孕組內(nèi)鮮胚組(16例)與凍胚組(10例)新生兒出生缺陷率也無差異(p0.05)。結(jié)論:1、助孕組多胎率較高,孕周較小,新生兒出生體重較低。2、單胎比較,助孕組NICU、低體重兒以及新生兒住院的概率較高。3、雙胎比較,助孕組低體重兒以及新生兒住院率較低,后代平均體重較高。4、助孕組內(nèi)鮮胚組低體重兒率較高,平均出生體重較低。5、助孕組與對照組新生兒出生缺陷無差異。
[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.
【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R714.8

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