HBV感染对人工辅助生殖的影响及其防范对策
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摘要
我国越来越多HBV感染的不孕夫妇选择人工辅助生殖技术(ART)方式行助孕治疗。HBV感染对ART实施过程以及子代健康状况的影响尚无定论。从女性及男性生殖细胞、实验环境、妊娠结局和对子代健康等方面出发综述了HBV感染对ART的影响,并探讨HBV感染者实施ART的防范对策,为制订科学的管理制度、预防疾病的传播提供支持。
Hepatitis B virus( HBV) infection is prevalent in China. With the rapid development of assisted reproductive technology( ART)in recent years,more and more couples with infertility and HBV infection choose ART to promote pregnancy. No conclusion has been reached on the influence of HBV infection on ART procedure and the health status of offspring. This article reviews the influence of HBV infection on ART from the aspects of sperm and oocyte function,laboratory environment,pregnancy outcome,and health of offspring and discusses the prevention measures during ART for people with HBV infection,in order to provide a reference for developing scientific management systems and preventing disease transmission.
Hepatitis B virus( HBV) infection is prevalent in China. With the rapid development of assisted reproductive technology( ART)in recent years,more and more couples with infertility and HBV infection choose ART to promote pregnancy. No conclusion has been reached on the influence of HBV infection on ART procedure and the health status of offspring. This article reviews the influence of HBV infection on ART from the aspects of sperm and oocyte function,laboratory environment,pregnancy outcome,and health of offspring and discusses the prevention measures during ART for people with HBV infection,in order to provide a reference for developing scientific management systems and preventing disease transmission.
引文
[1]World Health Organization.Global hepatitis report 2017[R].Geneva:WHO,2017.
[2]PIOMBONI P,BACCETTI B.Spermatozoon as a vehicle for HIV-1 and other viruses:A review[J].Mol Reprod Dev,2000,56(Suppl 2):238-242.
[3]LUTGENS SP,NELISSEN EC,van LOO IH,et al.To do or not to do:IVF and ICSI in chronic hepatitis B virus carriers[J].Hum Reprod,2009,24(11):2676-2678.
[4]VICARI E,ARCORIA D,DI MAURO C,et al.Sperm output in patients with primary infertility and hepatitis B or C virus;negative influence of HBV infection during concomitant varicocele[J].Minerva Med,2006,97(1):65-77.
[5]KANG W,LI Q,SHEN L,et al.Risk factors related to the failure of prevention of hepatitis B virus mother-to-child transmission in Yunnan,China[J].Vaccine,2017,35(4):605-609.
[6]MACHAIRA M,PAPAEVANGELOU V,VOULOUMANOU EK,et al.Hepatitis B vaccine alone or with hepatitis B immunoglobulin in neonates of HBsAg+/HBe Ag-mothers:A systematic review and meta-analysis[J].J Antimicrob Chemother,2015,70(2):396-404.
[7]SHI L,LIU S,ZHAO W,et al.Hepatitis B virus infection reduces fertilization ability during in vitro fertilization and embryo transfer[J].J Med Virol,2014,86(7):1099-1104.
[8]LEE VC,NG E HY,YEUNG WS,et al.Impact of positive hepatitis B surface antigen on the outcome of IVF treatment[J].Reprod Biomed Online,2010,21(5):712-717.
[9]ZHOU XP.Integration of hepatitis B virus DNA in human oocyte and embryo and outcome of assisted reproductive technology in women with hepatitis B virus infection[D].Hangzhou:Zhejiang University,2011.(in Chinese)周旭平.乙型肝炎病毒DNA在人卵母细胞和胚胎中的整合及HBV感染妇女ART结局的研究[D].杭州:浙江大学,2011.
[10]LIU L,LIU Q,WEN YQ,et al.Ovarian reserve function in infertile women with HBV infection[J].J Reproduct Med,2016,25(1):27-31.(in Chinese)柳榴,刘倩,文妍琪,等.不孕妇女乙肝病毒感染者的卵巢储备功能研究[J].生殖医学杂志,2016,25(1):27-31.
[11]YE F,YUE Y,LI S,et al.Presence of HBsAg,HBcAg,and HBVDNA in ovary and ovum of the patients with chronic hepatitis B virus infection[J].Am J Obstet Gynecol,2006,194(2):387-392.
[12]NIE R,JIN L,ZHANG H,et al.Presence of hepatitis B virus in oocytes and embryos:A risk of hepatitis B virus transmission during in vitro fertilization[J].Fertil Steril,2011,95(5):1667-1671.
[13]HU XL,ZHOU XP,QIAN YL,et al.The presence and expression of the hepatitis B virus in human oocytes and embryos[J].Hum Reprod,2011,26(7):1860-1867.
[14]BU Z,KONG H,LI J,et al.Effect of male hepatitis B virus infection on outcomes of in vitro fertilization and embryo transfer treatment:Insights from couples undergoing oocyte donation[J].Int J Clin Exp Med,2014,7(7):1860.
[15]CHEN HY,SHEN DX,WANG SH,et al.Detection on presence of hepatitis B virus in human infected by vertical transmission[J].China Public Health,2002,18(4):417-419.(in Chinese)陈怀宇,申东翔,王少华,等.乙型肝炎病毒垂直传播在人早期胚胎感染的检测[J].中国公共卫生,2002,18(4):417-419.
[16]HUANG TH,ZHANG QJ,XIE QD,et al.Presence and integration of HBV DNA in mouse oocytes[J].World J Gastroenterol,2005,11(19):2869.
[17]HADCHOUEL M,SCOTTO J,HURET JL,et al.Presence of HBVDNA in spermatozoa:A possible vertical transmission of HBV via the germ line[J].J Med Virol,1985,16(1):61-66.
[18]HUANG JM,HUANG TH,QIU HY,et al.Effects of hepatitis Bvirus infection on human sperm chromosomes[J].World JGastroenterol,2003,9(4):736.
[19]LORUSSO F,PALMISANO M,CHIRONNA M,et al.Impact of chronic viral diseases on semen parameters[J].Andrologia,2010,42(2):121-126.
[20]HUANG JM,HUANG TH,QIU HY,et al.Studies on the integration of hepatitis B virus DNA sequence in human sperm chromosomes[J].Asian J androl,2002,4(3):209-212.
[21]YE F,LIN SM,JIN Y,et al.Relationship between the expression of HBV mRNA in embryos and father-to-infant HBVtransmission[J].National J Androl,2013,19(5):429-433.(in Chinese)叶峰,蔺淑梅,金燕,等.胚胎中HBV mRNA的表达与父婴传播关系的研究[J].中华男科学杂志,2013,19(5):429-433.
[22]QIAN L,LI Q,LI H.Effect of hepatitis B virus infection on sperm quality and oxidative stress state of the semen of infertile males[J].American J Reprod Immunol,2016,76(3):183-185.
[23]ZHOU XP,HU XL,ZHU YM,et al.Comparison of semen quality and outcome of assisted reproductive techniques in Chinese men with and without hepatitis B[J].Asian J Androl,2011,13(3):465-469.
[24]OGER P,YAZBECK C,GERVAIS A,et al.Adverse effects of hepatitis B virus on sperm motility and fertilization ability during IVF[J].Reprod Biomed Online,2011,23(2):207-212.
[25]KANG XJ,XIE QD,ZHOU XL,et al.Effects of hepatitis B virus S protein exposure on sperm membrane integrity and functions[J].PLo S One,2012,7(3):e33471.
[26]HUANG JH,ZHONG Y,FANG XW,et al.Hepatitis B virus s protein enhances sperm apoptosis and reduces sperm fertilizing capacity in vitro[J].PLo S One,2013,8(7):e68688.
[27]LAM PM,SUEN SH,LAO TT,et al.Hepatitis B infection and outcomes of in vitro fertilization and embryo transfer treatment[J].Fertil Steril,2010,93(2):480-485.
[28]AJAYI AB,OLADOKUN A,BELLO FA,et al.Viral infections among couples for assisted reproduction in a fertility clinic in Nigeria[J].Niger J Clin Pract,2013,16(3):352-355.
[29]LIU H,LI GP,ZHANG LY.Risk of viral transmission and pregnancy outcome in patients with hepatitis B or hepatitis C during the implementation of assisted reproductive technology[J].Chin J Obstetr Gynecol,2007,42(11):784-786.(in Chinese)刘浩,李国屏,张丽燕.乙型和丙型肝炎患者实施辅助生殖技术中病毒传播风险和妊娠结局[J].中华妇产科杂志,2007,42(11):784-786.
[30]LIU L,WEN YQ,ZHAO M,et al.Effect of hepatitis B virus infection on assisted reproductive technology[J].J Reproduct Med,2015,24(12):1047-1050.(in Chinese)柳榴,文妍琪,赵萌,等.乙型肝炎病毒感染对辅助生殖技术的影响与探究[J].生殖医学杂志,2015,24(12):1047-1050.
[31]POCATE-CHERIET K,HEILIKMAN I,PORCHER R,et al.Predicting the clinical outcome of ICSI by sperm head vacuole examination[J].Syst Biol Reprod Mec,2017,63(1):29-36.
[32]PIRWANY IR,PHILLIPS S,KELLY S,et al.Reproductive performance of couples discordant for hepatitis B and C fol owing IVFtreatment[J].J Assist Reprod Gen,2004,21(5):157-161.
[33]HUANG HS.Maternal and fetal outcome in hepatitis B virus carriers receiving assisted reproductive technology[D].Hang zhou:Zhejiang University,2016.(in Chinese)黄昊舒.乙肝病毒携带者行辅助生育技术受孕后的母婴结局[D].杭州:浙江大学,2016.
[34]NI LL.Outcome of in vitro fertilization and mother-child health status in hepatitis B virus carriers[D].Hangzhou:Zhejiang University,2009.(in Chinese)倪丽莉.乙肝病毒携带者体外受精结局及母子健康状况分析[D].杭州:浙江大学,2009.
[35]HAO DY,YANG Y,ZHAO JL,et al.Vertical transmission risk of hepatitis B virus infection in children born to hepatitis B virnsinfected parent(s)after in vitro fertilization[J].Chin J Infect Dis,2016,34(5):271-273.(in Chinese)郝大勇,杨悦,赵君亮,等.乙型肝炎病毒感染者体外受精助孕后子代垂直传播风险[J].中华传染病杂志,2016,34(5):271-273.
[36]MOLINA I,del GONZALVO MC,CLAVERO A,et al.Assisted reproductive technology and obstetric outcome in couples when the male partner has a chronic viral disease[J].Int JFertil Steril,2014,7(4):291.
[37]WANG XL,ZHAO WD,CHEN ZZ,et al.Clinical value analysis of combined application of GnRH-a after laparoscopic adenomyomectomy[J].Chin J Modern Operative Surg,2017,21(6):454-457.(in Chinese)王晓丽,赵卫东,陈峥峥,等.腹腔镜下子宫腺肌病病灶切除术后联合应用GnRH-a的临床价值分析[J].中国现代手术学杂志,2017,21(6):454-457.
[38]Chinese Society of Hepatology and Chinese Society of Infectious Diseases,Chinese Medical Association.The guideline of prevention and treatment for chronic hepatitis B:A 2015 update[J].J Clin Hepatol,2015,31(12):1941-1960.(in Chinese)中华医学会肝病学分会,中华医学会感染病学分会.慢性乙型肝炎防治指南(2015年更新版)[J].临床肝胆病杂志,2015,31(12):1941-1960.
[39]XU X,SONG ML.The risk and prevention of transmission of hepatitis B virus in assisted reproductive technology[J].J Inter Reproduct Health/Family Planning,2012,31(1):17-19.(in Chinese)徐仙,宋梦玲.乙型肝炎患者实施辅助生殖技术中病毒传播的风险与防范[J].国际生殖健康/计划生育杂志,2012,31(1):17-19.
[40]SAUER MV,CHANG PL.Establishing a clinical program for human immunodeficiency virus 1-seropositive men to father seronegative children by means of in vitro fertilization with intracytoplasmic sperm injection[J].Am J Obstet Gynecol,2002,186(4):627-633.
[41]JINDAL SK,RAWLINS RG,MULLER CH,et al.Guidelines for risk reduction when handling gametes from infectious patients seeking assisted reproductive technologies[J].Reprod Biomed Online,2016,33(2):121-130.
[42]STEYAERT SR,LEROUX-ROELS GG,DHONT M.Infections in IVF:Review and guidelines[J].Hum Reprod update,2000,6(5):432-441.
[43]NIE R.Risk of HBV transmission during the implementation of assisted reproductive technology[D].Wuhan:Huazhong University of Science and Technology,2011.(in Chinese)聂睿.HBV在辅助生育技术中的传播风险[D].武汉:华中科技大学,2011.
[44]Obstetrics Subgroup,Chinese Society of Obstetrics and Gynecology,Chinese Medical Association.Clinical guidelines for the prevention of mother-to-child transmission of hepatitis Bvirus(1st edition)[J].Chin J Perinatal Med,2015,18(5):321-325.(in Chinese)中华医学会妇产科学分会产科学组.乙型肝炎病毒母婴传播预防临床指南(第1版)[J].中华围产医学杂志,2015,18(5):321-325.
[2]PIOMBONI P,BACCETTI B.Spermatozoon as a vehicle for HIV-1 and other viruses:A review[J].Mol Reprod Dev,2000,56(Suppl 2):238-242.
[3]LUTGENS SP,NELISSEN EC,van LOO IH,et al.To do or not to do:IVF and ICSI in chronic hepatitis B virus carriers[J].Hum Reprod,2009,24(11):2676-2678.
[4]VICARI E,ARCORIA D,DI MAURO C,et al.Sperm output in patients with primary infertility and hepatitis B or C virus;negative influence of HBV infection during concomitant varicocele[J].Minerva Med,2006,97(1):65-77.
[5]KANG W,LI Q,SHEN L,et al.Risk factors related to the failure of prevention of hepatitis B virus mother-to-child transmission in Yunnan,China[J].Vaccine,2017,35(4):605-609.
[6]MACHAIRA M,PAPAEVANGELOU V,VOULOUMANOU EK,et al.Hepatitis B vaccine alone or with hepatitis B immunoglobulin in neonates of HBsAg+/HBe Ag-mothers:A systematic review and meta-analysis[J].J Antimicrob Chemother,2015,70(2):396-404.
[7]SHI L,LIU S,ZHAO W,et al.Hepatitis B virus infection reduces fertilization ability during in vitro fertilization and embryo transfer[J].J Med Virol,2014,86(7):1099-1104.
[8]LEE VC,NG E HY,YEUNG WS,et al.Impact of positive hepatitis B surface antigen on the outcome of IVF treatment[J].Reprod Biomed Online,2010,21(5):712-717.
[9]ZHOU XP.Integration of hepatitis B virus DNA in human oocyte and embryo and outcome of assisted reproductive technology in women with hepatitis B virus infection[D].Hangzhou:Zhejiang University,2011.(in Chinese)周旭平.乙型肝炎病毒DNA在人卵母细胞和胚胎中的整合及HBV感染妇女ART结局的研究[D].杭州:浙江大学,2011.
[10]LIU L,LIU Q,WEN YQ,et al.Ovarian reserve function in infertile women with HBV infection[J].J Reproduct Med,2016,25(1):27-31.(in Chinese)柳榴,刘倩,文妍琪,等.不孕妇女乙肝病毒感染者的卵巢储备功能研究[J].生殖医学杂志,2016,25(1):27-31.
[11]YE F,YUE Y,LI S,et al.Presence of HBsAg,HBcAg,and HBVDNA in ovary and ovum of the patients with chronic hepatitis B virus infection[J].Am J Obstet Gynecol,2006,194(2):387-392.
[12]NIE R,JIN L,ZHANG H,et al.Presence of hepatitis B virus in oocytes and embryos:A risk of hepatitis B virus transmission during in vitro fertilization[J].Fertil Steril,2011,95(5):1667-1671.
[13]HU XL,ZHOU XP,QIAN YL,et al.The presence and expression of the hepatitis B virus in human oocytes and embryos[J].Hum Reprod,2011,26(7):1860-1867.
[14]BU Z,KONG H,LI J,et al.Effect of male hepatitis B virus infection on outcomes of in vitro fertilization and embryo transfer treatment:Insights from couples undergoing oocyte donation[J].Int J Clin Exp Med,2014,7(7):1860.
[15]CHEN HY,SHEN DX,WANG SH,et al.Detection on presence of hepatitis B virus in human infected by vertical transmission[J].China Public Health,2002,18(4):417-419.(in Chinese)陈怀宇,申东翔,王少华,等.乙型肝炎病毒垂直传播在人早期胚胎感染的检测[J].中国公共卫生,2002,18(4):417-419.
[16]HUANG TH,ZHANG QJ,XIE QD,et al.Presence and integration of HBV DNA in mouse oocytes[J].World J Gastroenterol,2005,11(19):2869.
[17]HADCHOUEL M,SCOTTO J,HURET JL,et al.Presence of HBVDNA in spermatozoa:A possible vertical transmission of HBV via the germ line[J].J Med Virol,1985,16(1):61-66.
[18]HUANG JM,HUANG TH,QIU HY,et al.Effects of hepatitis Bvirus infection on human sperm chromosomes[J].World JGastroenterol,2003,9(4):736.
[19]LORUSSO F,PALMISANO M,CHIRONNA M,et al.Impact of chronic viral diseases on semen parameters[J].Andrologia,2010,42(2):121-126.
[20]HUANG JM,HUANG TH,QIU HY,et al.Studies on the integration of hepatitis B virus DNA sequence in human sperm chromosomes[J].Asian J androl,2002,4(3):209-212.
[21]YE F,LIN SM,JIN Y,et al.Relationship between the expression of HBV mRNA in embryos and father-to-infant HBVtransmission[J].National J Androl,2013,19(5):429-433.(in Chinese)叶峰,蔺淑梅,金燕,等.胚胎中HBV mRNA的表达与父婴传播关系的研究[J].中华男科学杂志,2013,19(5):429-433.
[22]QIAN L,LI Q,LI H.Effect of hepatitis B virus infection on sperm quality and oxidative stress state of the semen of infertile males[J].American J Reprod Immunol,2016,76(3):183-185.
[23]ZHOU XP,HU XL,ZHU YM,et al.Comparison of semen quality and outcome of assisted reproductive techniques in Chinese men with and without hepatitis B[J].Asian J Androl,2011,13(3):465-469.
[24]OGER P,YAZBECK C,GERVAIS A,et al.Adverse effects of hepatitis B virus on sperm motility and fertilization ability during IVF[J].Reprod Biomed Online,2011,23(2):207-212.
[25]KANG XJ,XIE QD,ZHOU XL,et al.Effects of hepatitis B virus S protein exposure on sperm membrane integrity and functions[J].PLo S One,2012,7(3):e33471.
[26]HUANG JH,ZHONG Y,FANG XW,et al.Hepatitis B virus s protein enhances sperm apoptosis and reduces sperm fertilizing capacity in vitro[J].PLo S One,2013,8(7):e68688.
[27]LAM PM,SUEN SH,LAO TT,et al.Hepatitis B infection and outcomes of in vitro fertilization and embryo transfer treatment[J].Fertil Steril,2010,93(2):480-485.
[28]AJAYI AB,OLADOKUN A,BELLO FA,et al.Viral infections among couples for assisted reproduction in a fertility clinic in Nigeria[J].Niger J Clin Pract,2013,16(3):352-355.
[29]LIU H,LI GP,ZHANG LY.Risk of viral transmission and pregnancy outcome in patients with hepatitis B or hepatitis C during the implementation of assisted reproductive technology[J].Chin J Obstetr Gynecol,2007,42(11):784-786.(in Chinese)刘浩,李国屏,张丽燕.乙型和丙型肝炎患者实施辅助生殖技术中病毒传播风险和妊娠结局[J].中华妇产科杂志,2007,42(11):784-786.
[30]LIU L,WEN YQ,ZHAO M,et al.Effect of hepatitis B virus infection on assisted reproductive technology[J].J Reproduct Med,2015,24(12):1047-1050.(in Chinese)柳榴,文妍琪,赵萌,等.乙型肝炎病毒感染对辅助生殖技术的影响与探究[J].生殖医学杂志,2015,24(12):1047-1050.
[31]POCATE-CHERIET K,HEILIKMAN I,PORCHER R,et al.Predicting the clinical outcome of ICSI by sperm head vacuole examination[J].Syst Biol Reprod Mec,2017,63(1):29-36.
[32]PIRWANY IR,PHILLIPS S,KELLY S,et al.Reproductive performance of couples discordant for hepatitis B and C fol owing IVFtreatment[J].J Assist Reprod Gen,2004,21(5):157-161.
[33]HUANG HS.Maternal and fetal outcome in hepatitis B virus carriers receiving assisted reproductive technology[D].Hang zhou:Zhejiang University,2016.(in Chinese)黄昊舒.乙肝病毒携带者行辅助生育技术受孕后的母婴结局[D].杭州:浙江大学,2016.
[34]NI LL.Outcome of in vitro fertilization and mother-child health status in hepatitis B virus carriers[D].Hangzhou:Zhejiang University,2009.(in Chinese)倪丽莉.乙肝病毒携带者体外受精结局及母子健康状况分析[D].杭州:浙江大学,2009.
[35]HAO DY,YANG Y,ZHAO JL,et al.Vertical transmission risk of hepatitis B virus infection in children born to hepatitis B virnsinfected parent(s)after in vitro fertilization[J].Chin J Infect Dis,2016,34(5):271-273.(in Chinese)郝大勇,杨悦,赵君亮,等.乙型肝炎病毒感染者体外受精助孕后子代垂直传播风险[J].中华传染病杂志,2016,34(5):271-273.
[36]MOLINA I,del GONZALVO MC,CLAVERO A,et al.Assisted reproductive technology and obstetric outcome in couples when the male partner has a chronic viral disease[J].Int JFertil Steril,2014,7(4):291.
[37]WANG XL,ZHAO WD,CHEN ZZ,et al.Clinical value analysis of combined application of GnRH-a after laparoscopic adenomyomectomy[J].Chin J Modern Operative Surg,2017,21(6):454-457.(in Chinese)王晓丽,赵卫东,陈峥峥,等.腹腔镜下子宫腺肌病病灶切除术后联合应用GnRH-a的临床价值分析[J].中国现代手术学杂志,2017,21(6):454-457.
[38]Chinese Society of Hepatology and Chinese Society of Infectious Diseases,Chinese Medical Association.The guideline of prevention and treatment for chronic hepatitis B:A 2015 update[J].J Clin Hepatol,2015,31(12):1941-1960.(in Chinese)中华医学会肝病学分会,中华医学会感染病学分会.慢性乙型肝炎防治指南(2015年更新版)[J].临床肝胆病杂志,2015,31(12):1941-1960.
[39]XU X,SONG ML.The risk and prevention of transmission of hepatitis B virus in assisted reproductive technology[J].J Inter Reproduct Health/Family Planning,2012,31(1):17-19.(in Chinese)徐仙,宋梦玲.乙型肝炎患者实施辅助生殖技术中病毒传播的风险与防范[J].国际生殖健康/计划生育杂志,2012,31(1):17-19.
[40]SAUER MV,CHANG PL.Establishing a clinical program for human immunodeficiency virus 1-seropositive men to father seronegative children by means of in vitro fertilization with intracytoplasmic sperm injection[J].Am J Obstet Gynecol,2002,186(4):627-633.
[41]JINDAL SK,RAWLINS RG,MULLER CH,et al.Guidelines for risk reduction when handling gametes from infectious patients seeking assisted reproductive technologies[J].Reprod Biomed Online,2016,33(2):121-130.
[42]STEYAERT SR,LEROUX-ROELS GG,DHONT M.Infections in IVF:Review and guidelines[J].Hum Reprod update,2000,6(5):432-441.
[43]NIE R.Risk of HBV transmission during the implementation of assisted reproductive technology[D].Wuhan:Huazhong University of Science and Technology,2011.(in Chinese)聂睿.HBV在辅助生育技术中的传播风险[D].武汉:华中科技大学,2011.
[44]Obstetrics Subgroup,Chinese Society of Obstetrics and Gynecology,Chinese Medical Association.Clinical guidelines for the prevention of mother-to-child transmission of hepatitis Bvirus(1st edition)[J].Chin J Perinatal Med,2015,18(5):321-325.(in Chinese)中华医学会妇产科学分会产科学组.乙型肝炎病毒母婴传播预防临床指南(第1版)[J].中华围产医学杂志,2015,18(5):321-325.