乙肝病毒携带者行辅助生育技术受孕后的母婴结局

发布时间：2018-03-28 16:04

  本文选题：乙型肝炎病毒　切入点：垂直传播　出处：《浙江大学》2016年硕士论文

【摘要】：背景目前全世界有超过4亿的人群为慢性乙型肝炎病毒携带者,而我国属于乙肝高度流行的地区。其主要的传播途径为垂直传播,其次经血制品、体液、医疗等途径传播。如果不进行免疫干预,85～90%血清HBsAg、HBeAg双阳性的母亲会传播给子代,其中90%将发展为慢性乙肝病毒携带者。辅助生殖技术的历史已经历了30余年,随着近年来辅助生育技术的发展,越来越多患有不孕不育症的HBV携带者选择体外受精(IVF)或卵胞浆内单精子显微注射技术(ICSI)及胚胎移植的方式辅助生育。针对HBV不孕夫妇实施ART后的母婴健康问题的随访研究并不多。HBV通过辅助生育技术进行传播的风险,目前仍不清楚。有研究认为冷冻精子保存,精子洗涤,胚胎处于氮蒸汽状态,双密封低温容器的处理技术可以降低HBV感染的比例。还有研究发现HBV感染的男性精子质量相对较差,对受精率、胚胎着床率、受孕几率、孕周都有一定程度的影响。目的调查乙肝病毒携带者的ART实施情况、母亲妊娠期并发症情况、子代的健康状况以及HBV免疫预防情况,与同期非HBV携带者的妊娠状况以及国内外HBV携带者的自然妊娠资料做比较,观察三者之间是否存在差异并探究其相关的影响因素,为以后的辅助生育工作提供参考。方法选择2010年期间在浙江大学附属妇产科医院生殖内分泌科住院行辅助生育技术助孕后成功妊娠的乙肝病毒携带者不孕不育夫妇(共265对)作为研究对象。然后建立登记表《《HBV携带者ART实施状况及母婴健康状况》,记录夫妻双方的一般信息、ART实施情况、妊娠期情况、分娩及产后情况、新生儿情况、免疫防治情况。选取本院非HBV携带者ART人群以及HBV携带者的自然妊娠资料作为对照。用SPSS 20.0统计软件分析对比调查结果。结果1.孕妇妊娠期及分娩情况：1.1总体情况：乙肝携带者夫妇中216例成功分娩(81.51%)；59例为早产(23.61%)；186例行剖宫产(86.11%)；发生异位妊娠有13例(4.91%)；36例自然流产(13.58%)。子代总数282例,其中单胎151例,双胎64例,三胎1例；男孩141名,女孩141名。男女比例为100：100。HBV携带者与非HBV携带行ART后的成功分娩率(80.5%)、早产率(21.24%)、剖宫产率(83.9%)、异位妊娠率(5.99%)、流产率(13.51%)、单胎率(71.66%)、双胎率(28.34%)及男女比例(101.70：100)相比较均无明显差异(P0.05)。根据流行病学资料显示自然妊娠剖宫产率(35-45%)及双胎率(1.62%)要低于实施ART的人群。HBV携带者实施IVF子代多胎率(30.87%)与ICSI子代多胎率(28.36%)比较无显著性差异(P0.05)o HBV携带者孕妇的剖宫产率(86.11%)、早产率(23.61%)与普通ART后孕妇剖宫产率(83.8%)和早产率(19.97%)相比均无明显差异(P0.05),但数值上高于HBV携带者自然妊娠数据(剖宫产率44-54%、早产率11.91%)。仅HBsAg阳性的孕妇的剖宫产率(81.40%)与HBsAg、HBeAg均阳性孕妇的剖宫产率(72.22%)比较无明显差异(P0.05)。1.2 HBV携带者行ART后孕妇妊娠期并发症情况：OHSS发生率5.12%；孕早期先兆流产9.28%；妊娠剧吐1.03%；贫血11.34%；妊娠期高血压疾病(PIH)5.15%；妊娠期糖尿病(GDM)6.67%；妊娠期肝内胆汁淤积症(ICP)6.19%；肝功能损害4.64%；前置胎盘1.03%；胎盘早剥1.55%；胎膜早破6.19%；羊水过少5.67%；羊水过多1.55%；耻骨联合分离0.52%；脐带绕颈8.76%；宫内窘迫9.28%。在数值上,HBV携带者自然妊娠流行病学数据显示羊水过少(0.4-4%)、羊水过多(0.5-1%)的发生率低于行ART后的HBV携带者；而贫血(30-50%)、肝损(25-40.7%)、胎膜早破(12-25.2%)、脐带绕颈(10.5-20%)高于行ART后的HBV携带者；非HBV携带的ART人群流行病学数据显示PIH(11-22%)、前置胎盘(4.5-6.9%)发生率高于行ART后的HBV携带者；其他妊娠期并发症的发病率均与流行病学数据相符。2.子代健康状况：2.1子代HBV感染情况：2010年我院HBV携带者(除其他感染期)行ART后产下子代251名,49名失访,出生时查“乙肝三系”或HBV DNA提示感染者共11名。仅女方女方携带与仅男方携带形式之间的子代感染率比较无明显差异(P0.05); HBsAg、 HBeAg双阳性携带者行ART后子代的感染率(17.1%)明显高于仅HBsAg阳性的携带者的子代感染率(3.37%) (P=0.023)。HBV携带者行IVF方式受精后子代感染率(7/161)与ICSI方式受精后子代感染率(4/69)比较无显著性差异(P0.05)。分别比较HBsAg阳性和HBsAg+HBeAg阳性携带者行剖宫产的子代感染率(2.13%、12.5%)与平产孕妇的子代感染率(12.5%、16.67%)比较无显著性差异(P0.05)。低体重儿的HBV感染率(3.51%)与非低体重儿的HBV感染率无显著差异(P0.05)。发生新生儿窒息的子代HBV感染率(14.29%)与未发生新生儿窒息的子代HBV感染率(4.15%)比较无显著差异(P0.05)。2.2子代出生缺陷与新生儿疾病：HBV携带者于我院行ICSI受精的子代出生缺陷(5/69)发生率显著高于行IVF受精的子代(2/161)(P=0.044)。我院HBV携带者实施ART后子代平均出生体重2887.7+614.67克,单胎平均出生体重(3257.5±504.91 1克)显著高于双胎平均出生体重(2460.2±423.62克)(P0.01)。其中低出生体重儿22.7%,极低出生体重儿1.77%。多胎妊娠的低出生体重儿的比例(60/131)显著高于单胎妊娠的低出生体重儿的比例(5/151)(P0.01)。早产儿的新生儿窒息率(16.88%)显著高于足月儿的新生儿窒息率(0.65%)(P0.01)。HBV携带者的子代中出生时发生新生儿呼吸窘迫综合症(NRDs)比例(0.87%)低于自然妊娠资料,黄疽发生率(10.39%)高于自然妊娠资料,感染性疾病发生率(3.46%)与自然妊娠资料相符,先天畸形发生率(3.03%)低于自然妊娠资料。3.HBV免疫预防情况HBsAg、HBeAg双阳性携带者行ART后妊娠期HBIG注射率(61.54%)与仅HBsAg阳性的携带者HBIG注射率(55.17%)比较注射率无明显差异(P0.05)。分别比较HBsAg阳性和HBsAg+HBAg阳性携带者实施HBIG阻断后的子代感染率(0%、13.33%)与未实施HBIG阻断的子代感染率(7.69%、14.29%)无显著性差异(P0.05)。结论1.乙肝病毒的携带与否并不影响ART的成功分娩率、早产率、异位妊娠率、流产率、剖宫产率子代多胎率及男女比例。2.HBV携带者实施ART不会明显增加妊娠期并发症的发生率。3.HBsAg+HBeAg双阳性的携带者行ART后子代感染HBV的风险高于仅HBsAg阳性的携带者,与采取的受精方式(IVF或ICSI)无明显相关性。4.HBV携带母亲孕期注射HBIG不能显著降低子代HBV的感染率。5.阴道分娩方式、低出生体重、新生儿窒息与HBV携带者实施ART后子代HBV感染均无明显相关性。6.HBV携带者实施ART不会显著增加子代出生缺陷发生率,但行ICSI方式受精的子代出生缺陷发生风险显著高于IVF受精方式。7.多胎妊娠会显著增加子代低出生体重的风险。8.早产儿的新生儿窒息发生风险显著高于足月儿。
[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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