本文選題：乙型肝炎病毒　切入點：垂直傳播　出處：《浙江大學(xué)》2016年碩士論文

【摘要】：背景目前全世界有超過4億的人群為慢性乙型肝炎病毒攜帶者,而我國屬于乙肝高度流行的地區(qū)。其主要的傳播途徑為垂直傳播,其次經(jīng)血制品、體液、醫(yī)療等途徑傳播。如果不進行免疫干預(yù),85～90%血清HBsAg、HBeAg雙陽性的母親會傳播給子代,其中90%將發(fā)展為慢性乙肝病毒攜帶者。輔助生殖技術(shù)的歷史已經(jīng)歷了30余年,隨著近年來輔助生育技術(shù)的發(fā)展,越來越多患有不孕不育癥的HBV攜帶者選擇體外受精(IVF)或卵胞漿內(nèi)單精子顯微注射技術(shù)(ICSI)及胚胎移植的方式輔助生育。針對HBV不孕夫婦實施ART后的母嬰健康問題的隨訪研究并不多。HBV通過輔助生育技術(shù)進行傳播的風(fēng)險,目前仍不清楚。有研究認為冷凍精子保存,精子洗滌,胚胎處于氮蒸汽狀態(tài),雙密封低溫容器的處理技術(shù)可以降低HBV感染的比例。還有研究發(fā)現(xiàn)HBV感染的男性精子質(zhì)量相對較差,對受精率、胚胎著床率、受孕幾率、孕周都有一定程度的影響。目的調(diào)查乙肝病毒攜帶者的ART實施情況、母親妊娠期并發(fā)癥情況、子代的健康狀況以及HBV免疫預(yù)防情況,與同期非HBV攜帶者的妊娠狀況以及國內(nèi)外HBV攜帶者的自然妊娠資料做比較,觀察三者之間是否存在差異并探究其相關(guān)的影響因素,為以后的輔助生育工作提供參考。方法選擇2010年期間在浙江大學(xué)附屬婦產(chǎn)科醫(yī)院生殖內(nèi)分泌科住院行輔助生育技術(shù)助孕后成功妊娠的乙肝病毒攜帶者不孕不育夫婦(共265對)作為研究對象。然后建立登記表《《HBV攜帶者ART實施狀況及母嬰健康狀況》,記錄夫妻雙方的一般信息、ART實施情況、妊娠期情況、分娩及產(chǎn)后情況、新生兒情況、免疫防治情況。選取本院非HBV攜帶者ART人群以及HBV攜帶者的自然妊娠資料作為對照。用SPSS 20.0統(tǒng)計軟件分析對比調(diào)查結(jié)果。結(jié)果1.孕婦妊娠期及分娩情況：1.1總體情況：乙肝攜帶者夫婦中216例成功分娩(81.51%)；59例為早產(chǎn)(23.61%)；186例行剖宮產(chǎn)(86.11%)；發(fā)生異位妊娠有13例(4.91%)；36例自然流產(chǎn)(13.58%)。子代總數(shù)282例,其中單胎151例,雙胎64例,三胎1例；男孩141名,女孩141名。男女比例為100：100。HBV攜帶者與非HBV攜帶行ART后的成功分娩率(80.5%)、早產(chǎn)率(21.24%)、剖宮產(chǎn)率(83.9%)、異位妊娠率(5.99%)、流產(chǎn)率(13.51%)、單胎率(71.66%)、雙胎率(28.34%)及男女比例(101.70：100)相比較均無明顯差異(P0.05)。根據(jù)流行病學(xué)資料顯示自然妊娠剖宮產(chǎn)率(35-45%)及雙胎率(1.62%)要低于實施ART的人群。HBV攜帶者實施IVF子代多胎率(30.87%)與ICSI子代多胎率(28.36%)比較無顯著性差異(P0.05)o HBV攜帶者孕婦的剖宮產(chǎn)率(86.11%)、早產(chǎn)率(23.61%)與普通ART后孕婦剖宮產(chǎn)率(83.8%)和早產(chǎn)率(19.97%)相比均無明顯差異(P0.05),但數(shù)值上高于HBV攜帶者自然妊娠數(shù)據(jù)(剖宮產(chǎn)率44-54%、早產(chǎn)率11.91%)。僅HBsAg陽性的孕婦的剖宮產(chǎn)率(81.40%)與HBsAg、HBeAg均陽性孕婦的剖宮產(chǎn)率(72.22%)比較無明顯差異(P0.05)。1.2 HBV攜帶者行ART后孕婦妊娠期并發(fā)癥情況：OHSS發(fā)生率5.12%；孕早期先兆流產(chǎn)9.28%；妊娠劇吐1.03%；貧血11.34%；妊娠期高血壓疾病(PIH)5.15%；妊娠期糖尿病(GDM)6.67%；妊娠期肝內(nèi)膽汁淤積癥(ICP)6.19%；肝功能損害4.64%；前置胎盤1.03%；胎盤早剝1.55%；胎膜早破6.19%；羊水過少5.67%；羊水過多1.55%；恥骨聯(lián)合分離0.52%；臍帶繞頸8.76%；宮內(nèi)窘迫9.28%。在數(shù)值上,HBV攜帶者自然妊娠流行病學(xué)數(shù)據(jù)顯示羊水過少(0.4-4%)、羊水過多(0.5-1%)的發(fā)生率低于行ART后的HBV攜帶者；而貧血(30-50%)、肝損(25-40.7%)、胎膜早破(12-25.2%)、臍帶繞頸(10.5-20%)高于行ART后的HBV攜帶者；非HBV攜帶的ART人群流行病學(xué)數(shù)據(jù)顯示PIH(11-22%)、前置胎盤(4.5-6.9%)發(fā)生率高于行ART后的HBV攜帶者；其他妊娠期并發(fā)癥的發(fā)病率均與流行病學(xué)數(shù)據(jù)相符。2.子代健康狀況：2.1子代HBV感染情況：2010年我院HBV攜帶者(除其他感染期)行ART后產(chǎn)下子代251名,49名失訪,出生時查“乙肝三系”或HBV DNA提示感染者共11名。僅女方女方攜帶與僅男方攜帶形式之間的子代感染率比較無明顯差異(P0.05); HBsAg、 HBeAg雙陽性攜帶者行ART后子代的感染率(17.1%)明顯高于僅HBsAg陽性的攜帶者的子代感染率(3.37%) (P=0.023)。HBV攜帶者行IVF方式受精后子代感染率(7/161)與ICSI方式受精后子代感染率(4/69)比較無顯著性差異(P0.05)。分別比較HBsAg陽性和HBsAg+HBeAg陽性攜帶者行剖宮產(chǎn)的子代感染率(2.13%、12.5%)與平產(chǎn)孕婦的子代感染率(12.5%、16.67%)比較無顯著性差異(P0.05)。低體重兒的HBV感染率(3.51%)與非低體重兒的HBV感染率無顯著差異(P0.05)。發(fā)生新生兒窒息的子代HBV感染率(14.29%)與未發(fā)生新生兒窒息的子代HBV感染率(4.15%)比較無顯著差異(P0.05)。2.2子代出生缺陷與新生兒疾�。篐BV攜帶者于我院行ICSI受精的子代出生缺陷(5/69)發(fā)生率顯著高于行IVF受精的子代(2/161)(P=0.044)。我院HBV攜帶者實施ART后子代平均出生體重2887.7+614.67克,單胎平均出生體重(3257.5±504.91 1克)顯著高于雙胎平均出生體重(2460.2±423.62克)(P0.01)。其中低出生體重兒22.7%,極低出生體重兒1.77%。多胎妊娠的低出生體重兒的比例(60/131)顯著高于單胎妊娠的低出生體重兒的比例(5/151)(P0.01)。早產(chǎn)兒的新生兒窒息率(16.88%)顯著高于足月兒的新生兒窒息率(0.65%)(P0.01)。HBV攜帶者的子代中出生時發(fā)生新生兒呼吸窘迫綜合癥(NRDs)比例(0.87%)低于自然妊娠資料,黃疽發(fā)生率(10.39%)高于自然妊娠資料,感染性疾病發(fā)生率(3.46%)與自然妊娠資料相符,先天畸形發(fā)生率(3.03%)低于自然妊娠資料。3.HBV免疫預(yù)防情況HBsAg、HBeAg雙陽性攜帶者行ART后妊娠期HBIG注射率(61.54%)與僅HBsAg陽性的攜帶者HBIG注射率(55.17%)比較注射率無明顯差異(P0.05)。分別比較HBsAg陽性和HBsAg+HBAg陽性攜帶者實施HBIG阻斷后的子代感染率(0%、13.33%)與未實施HBIG阻斷的子代感染率(7.69%、14.29%)無顯著性差異(P0.05)。結(jié)論1.乙肝病毒的攜帶與否并不影響ART的成功分娩率、早產(chǎn)率、異位妊娠率、流產(chǎn)率、剖宮產(chǎn)率子代多胎率及男女比例。2.HBV攜帶者實施ART不會明顯增加妊娠期并發(fā)癥的發(fā)生率。3.HBsAg+HBeAg雙陽性的攜帶者行ART后子代感染HBV的風(fēng)險高于僅HBsAg陽性的攜帶者,與采取的受精方式(IVF或ICSI)無明顯相關(guān)性。4.HBV攜帶母親孕期注射HBIG不能顯著降低子代HBV的感染率。5.陰道分娩方式、低出生體重、新生兒窒息與HBV攜帶者實施ART后子代HBV感染均無明顯相關(guān)性。6.HBV攜帶者實施ART不會顯著增加子代出生缺陷發(fā)生率,但行ICSI方式受精的子代出生缺陷發(fā)生風(fēng)險顯著高于IVF受精方式。7.多胎妊娠會顯著增加子代低出生體重的風(fēng)險。8.早產(chǎn)兒的新生兒窒息發(fā)生風(fēng)險顯著高于足月兒。
[Abstract]:The background of the world has more than 400 million people with chronic hepatitis B virus carriers, but our country belongs to the height of hepatitis B endemic area. The main route of transmission for vertical transmission, followed by blood products, body fluids, medical and other ways. If you do not spread the immune intervention, 85 ~ 90% HBsAg in serum, HBeAg positive mothers spread to the offspring, 90% of them will develop chronic hepatitis B virus carriers. The history of assisted reproductive technology has experienced more than 30 years, with the development of assisted reproductive technology in recent years, more and more HBV carriers selection of in vitro fertilization with infertility (IVF) or intracytoplasmic sperm injection (ICSI) assisted reproductive technology and embryo transfer way. Not many follow-up studies for maternal and child health problems HBV infertile couples after the implementation of ART.HBV through assisted reproductive technology to spread the risk, is still not clear. Study of frozen sperm storage, sperm washing, embryos in nitrogen vapor state, double sealing technology of the cryogenic vessel can reduce the infection rate of HBV and HBV infection. The study found that male sperm quality is relatively poor, the fertilization rate, implantation rate, pregnancy rate, have a certain degree of influence of gestational weeks. Objective to investigate hepatitis B virus carriers in the ART implementation period, the complications of maternal pregnancy, offspring health and HBV immunization, compared with the earlier pregnancy status at home and abroad as well as non HBV carriers with HBV natural pregnancy, whether there are differences were observed between the three and explore its related factors, and provide reference for assisted reproduction work for the future. Methods during 2010 in the Zhejiang University affiliated obstetrics and gynecology hospital admitted to the Department of Endocrinology for reproductive assisted reproductive technology help pregnant after successful pregnancy Hepatitis B virus carriers of infertile couples (265 pairs) as the research object. Then establish the registration table < general information records of both husband and wife, ART implementation, pregnancy, childbirth and postpartum, newborn, immune prevention. Select the non ART population and HBV carriers the natural pregnancy data with HBV as control in our hospital. The comparative analysis of the results of the survey with SPSS 20 statistical software. Results of the 1. pregnant women during pregnancy and childbirth: 1.1 general condition: 216 cases of hepatitis B carriers in a couple of successful delivery (81.51%); 59 cases of preterm birth (23.61%); 186 cases of cesarean section (86.11%) occurred; ectopic pregnancy in 13 cases (4.91%); 36 cases of spontaneous abortion (13.58%). The total number of offspring in 282 cases, including 151 cases of singleton, twins in 64 cases, 1 cases of three births; 141 boys, 141 girls. The sex ratio was 100:100.HBV 鎼哄甫鑰呬笌闈濰BV鎼哄甫琛孉RT鍚庣殑鎴愬姛鍒嗗ī鐜，

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