Application of Assisted Reproductive Technology in Hydatidiform Mole

doi:10.12280/gjszjk.20200612

Abstract

Abstract:

Hydatidiform mole (HM) is a common obstetric disease, which is classified as a gestational trophoblastic disease. HM is characterized by swollen villi. HM can be diagnosed and classified by clinical manifestations and histological examination. However, the complex classification and limitations of etiological knowledge of HM, in addition to the high risk of recurrence, make it difficult to prevent. With the development of sequencing technology, the assisted reproductive technology has been rapidly developed in recent years, especially the pre-implantation genetic testing. These technologies can be applied in the acquisition and evaluation of embryos in vitro. However, the application of assisted reproductive technology in HM patients is still confined due to the limitations of current understanding on HM. There are very limited knowledge on the prevention and reproductive guidance of HM, especially the recurrent HM. The epidemiology, clinical manifestations, histology and the genetic characteristics were reviewed in this article, while the application progress of assisted reproductive technology in HM was also discussed.

Key words: Hydatidiform mole, Gestational trophoblastic disease, NLR proteins, Reproductive techniques,assisted, Mutation

YANG Jing-yi, LIU Yan, ZHI Xu. Application of Assisted Reproductive Technology in Hydatidiform Mole[J]. Journal of International Reproductive Health/Family Planning, 2021, 40(3): 209-215.

Figures/Tables 2

References 38

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类型	MIM number （表型）	MIM number （基因）	遗传方式	基因名称	定位
Recurrent HM1	231090	609661	AR	NALP7	19q13.42
Recurrent HM2	614293	611687	AR	KHDC3L	6q13
Recurrent HM3	618431	608797	AR	MEI1	22q13.2
Recurrent HM4	618432	616109	-	C11orf80	11q13.2

类型	MIM number （表型）	MIM number （基因）	遗传方式	基因名称	定位
Recurrent HM1	231090	609661	AR	NALP7	19q13.42
Recurrent HM2	614293	611687	AR	KHDC3L	6q13
Recurrent HM3	618431	608797	AR	MEI1	22q13.2
Recurrent HM4	618432	616109	-	C11orf80	11q13.2

年份	内容	参考文献
1996年	该病例提示有复发性GTD病史的患者IVF更易形成三倍体受精卵。该病例中女方有2次复发GTD病史,其中1次组织病理学证实为CHM,1次临床诊断为宫角妊娠伴葡萄胎样改变。2次IVF-胚胎移植（ET）周期中形成三倍体胚胎的比例分别为21%和47%。	[31]
1997年	该病例是第一次将ICSI联合FISH技术应用到阻止复发性GTD发生的报道。该病例中女方因双侧输卵管堵塞行两次IVF,均因孕期β-hCG值异常人工终止妊娠。后经ICSI联合FISH技术,取卵MⅡ9枚,2PN 6枚,最终选取2枚男胚,移植后未孕。	[32]
2009年	该病例是第一次将ICSI和胚胎植入前的单倍型分析（preimplantation genetic haplotyping,PGH）应用到复发性父系来源CHM的报道,该病例中女方孕3产0（G3P0）,其中2次为葡萄胎病史,后经ICSI和STR技术,移植1枚胚胎后成功分娩出同卵双胎女婴。	[33]
2011年	该研究收集并分析了35例至少发生过1次葡萄胎的患者,其中7例携带NLRP7双等位基因变异,4例携带NLRP7杂合变异。该研究中3例携带NLRP7双等位基因变异的患者、2例携带NLRP7单基因变异的患者接受了辅助生殖技术治疗（PGT/PGH/FISH）。携带NLRP7双等位基因变异的患者未成功受孕,1例携带NLRP7单基因变异的患者接受了辅助生殖技术治疗后正常妊娠至24周（截止文章发表时）。	[6]
2017年	该研究是第一篇关于携带NLRP7基因变异患者早期体外胚胎发育的报道。该患者G5P0,5次葡萄胎病史,经筛查发现携带NLRP7纯合变异（c.2810+2T>G）。该病例中10枚胚胎均发育停滞在72~144 h。经胚胎植入前的遗传学筛查（preimplantation genetic screening,PGS）发现10枚胚胎中2枚为双亲来源整倍体,5枚为母源性三体,其余3枚均携带不确定的染色体异常。	[34]
2018年	中国一篇关于既往GTD病史的不孕患者行IVF/ICSI治疗的研究指出,虽然获卵数及可用胚胎数与无GTD史的继发不孕患者相比无差异,但是既往有GTD病史的患者移植日内膜厚度、移植后生化妊娠率、继续妊娠率都显著低于既往无GTD史的继发性不孕患者。	[35]
2018年	该研究中报道了1例33岁患者,有2次PHM病史和2次不明原因自然流产史,检测到患者携带KHDC3L纯合移码突变（c.44delA）,2次辅助生殖周期中所有胚胎均发育阻滞到D5/D6。	[24]
2020年	该研究中2例复发性葡萄胎患者行IVF-PGT。1例患者有6次葡萄胎病史,此次IVF经FISH检测13,18,21号染色体,没有可移植的胚胎,患者最终通过赠卵受孕。另1例患者有5次葡萄胎病史,此次IVF经FISH检测18号,X,Y染色体,最终移植了2枚XX[18] ×2的胚胎,后确诊为葡萄胎。	[36]

年份	内容	参考文献
1996年	该病例提示有复发性GTD病史的患者IVF更易形成三倍体受精卵。该病例中女方有2次复发GTD病史,其中1次组织病理学证实为CHM,1次临床诊断为宫角妊娠伴葡萄胎样改变。2次IVF-胚胎移植（ET）周期中形成三倍体胚胎的比例分别为21%和47%。	[31]
1997年	该病例是第一次将ICSI联合FISH技术应用到阻止复发性GTD发生的报道。该病例中女方因双侧输卵管堵塞行两次IVF,均因孕期β-hCG值异常人工终止妊娠。后经ICSI联合FISH技术,取卵MⅡ9枚,2PN 6枚,最终选取2枚男胚,移植后未孕。	[32]
2009年	该病例是第一次将ICSI和胚胎植入前的单倍型分析（preimplantation genetic haplotyping,PGH）应用到复发性父系来源CHM的报道,该病例中女方孕3产0（G3P0）,其中2次为葡萄胎病史,后经ICSI和STR技术,移植1枚胚胎后成功分娩出同卵双胎女婴。	[33]
2011年	该研究收集并分析了35例至少发生过1次葡萄胎的患者,其中7例携带NLRP7双等位基因变异,4例携带NLRP7杂合变异。该研究中3例携带NLRP7双等位基因变异的患者、2例携带NLRP7单基因变异的患者接受了辅助生殖技术治疗（PGT/PGH/FISH）。携带NLRP7双等位基因变异的患者未成功受孕,1例携带NLRP7单基因变异的患者接受了辅助生殖技术治疗后正常妊娠至24周（截止文章发表时）。	[6]
2017年	该研究是第一篇关于携带NLRP7基因变异患者早期体外胚胎发育的报道。该患者G5P0,5次葡萄胎病史,经筛查发现携带NLRP7纯合变异（c.2810+2T>G）。该病例中10枚胚胎均发育停滞在72~144 h。经胚胎植入前的遗传学筛查（preimplantation genetic screening,PGS）发现10枚胚胎中2枚为双亲来源整倍体,5枚为母源性三体,其余3枚均携带不确定的染色体异常。	[34]
2018年	中国一篇关于既往GTD病史的不孕患者行IVF/ICSI治疗的研究指出,虽然获卵数及可用胚胎数与无GTD史的继发不孕患者相比无差异,但是既往有GTD病史的患者移植日内膜厚度、移植后生化妊娠率、继续妊娠率都显著低于既往无GTD史的继发性不孕患者。	[35]
2018年	该研究中报道了1例33岁患者,有2次PHM病史和2次不明原因自然流产史,检测到患者携带KHDC3L纯合移码突变（c.44delA）,2次辅助生殖周期中所有胚胎均发育阻滞到D5/D6。	[24]
2020年	该研究中2例复发性葡萄胎患者行IVF-PGT。1例患者有6次葡萄胎病史,此次IVF经FISH检测13,18,21号染色体,没有可移植的胚胎,患者最终通过赠卵受孕。另1例患者有5次葡萄胎病史,此次IVF经FISH检测18号,X,Y染色体,最终移植了2枚XX[18] ×2的胚胎,后确诊为葡萄胎。	[36]