反覆流產：修订间差异

反覆流產; Recurrent miscarriage
同义词	習慣性流產（habitual abortion），復發性流產（recurrent pregnancy loss, RPL）
分类和外部资源
醫學專科	產科學
ICD-11	GA33
ICD-10	N96
eMedicine	260495
	[编辑此条目的维基数据]

交互式浏览历史

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2019年11月2日 (六) 16:01的版本

反覆流產（recurrent miscarriage）是指兩次或兩次以上連續流產^[1]，過去稱為習慣性流產（habitual abortion），而在醫學研究中較常使用復發性流產（recurrent pregnancy loss 或 RPL）。造成不孕症無法懷孕的原因各有不同，然而許多反覆流產的原因仍不清楚。美國生殖醫學學會建議在三次或三次以上流產發生後應進行完整評估^[2]。嘗試生育的夫婦中約 1％有反覆流產的問題^[3]^[4]。

原因

反覆流產的原因多樣，有些可以治療。有些夫婦不曾找到真正的原因，且通常需要大量的檢查^[5]。約有 50-75％的反覆流產患者找不到病因^[2]。

生活方式

雖然一般來說，生活方式與流產風險增加有關，通常不將它列為 RPL 的特定原因，但應盡力協助 RPL 患者解決這些問題。需要特別關注的是長期接觸的毒害，如：吸菸、酒精和藥物^[6]。

解剖結構

經歷過三次或更多次反覆流產的婦女中 15％有的解剖學上的結構缺陷，這些結構缺陷會使妊娠期無法完全進行到順利生產^[7]。子宮結構會影響胎兒能否孕育到足月。解剖學上的結構變異很常見，且可能是先天^{[來源請求]}。

子宮結構的類型	流產率	參考文獻
雙角子宮	40–79%	^[8]^[9]
子宮縱隔或單角子宮	34–88%	^[8]^[10]
弓形子宮	未知	^[8]^[10]
雙子宮畸形	40%	^[8]^[10]
子宮肌瘤	未知	^[10]

子宮頸

在第二孕期，子宮頸沒力或閉鎖不全的問題可能會反覆發生。這種宮頸機能不全，使子宮頸在整個懷孕期間無法保持閉合狀態^[11]^[12]，並導致流產或早產^{[來源請求]}。

染色體異常

易位

配偶之一中有染色體易位或羅伯遜易位（英语：Robertsonian translocation）會導致胎兒無法生存且最終流產。所以，若是婦女發生反覆流產，伴侶雙方都需要進行核型染色體檢查^[13]。

反覆流產之中大約 3％是因為父母一方或雙方有染色體異常。儘管患有此類染色體異常者更容易流產，但他們也可能生下正常或異常的嬰兒^{[來源請求]}。

非整倍體

非整倍體可能造成隨機的自發性流產以及反覆流產^[6]。非整倍體在高齡備孕者更普遍，代表生殖細胞品質不佳^[14]^[15]。

內分泌疾病

患甲狀腺機能低下症的婦女流產風險會增加。未診斷或控制不佳的糖尿病也會增加流產風險。多囊卵巢綜合症的流產率也較高，可能與高胰島素血症或雄激素過多有關。黃體期的孕酮分泌不足也可能為 RPL 拉開序幕（見下文）。

易栓症

易栓症（英语：thrombophilia）（具有容易血栓形成的體質）可能是造成婦女反覆流產的重要原因之一。最常見的問題是第五凝血因子萊頓變異（英语：factor V Leiden）和凝血酶原 G20210A（英语：prothrombin G20210A）的基因突變^[6]。一些初步研究認為抗凝劑可能會增加懷孕至足月的機會，但是這些研究仍需要更多研究印證才能在臨床廣泛應用^[16]。需注意，許多易栓症婦女未經治療也完成一次或多次懷孕，但也有其他人出現妊娠併發症。易栓症可解釋 49–65％的反覆流產^[17]。

免疫因素

因免疫因素導致反覆流產的共同特徵是母親對胎兒的孕期免疫耐受性（英语：Immune tolerance in pregnancy）降低^[18]。

抗磷脂症候群

抗磷脂症候群是一種自體免疫疾病，是反覆流產的常見原因之一^[4]^[6]。大約 15％反覆流產婦女有高濃度的抗磷脂抗體^[4]。在「第一孕期發生兩次或兩次以上流產」或是「第二孕期發生一次或一次以上流產」的婦女，可能需要做血液抗體檢測排除抗磷脂症候群的可能^[4]。被診斷抗磷脂症候群的婦女在之後的懷孕中通常需要接受阿司匹林或肝素的治療，但因為缺乏高品質研究，是否治療仍有爭議^[19]^[20]。

甲狀腺抗體

抗甲狀腺自體抗體與反覆流產有關，風險增加（勝算比（英语：odds ratio））2.3 倍，95% 信賴區間 1.5–3.5^[21]。

子宮內的自然殺手細胞增多

自然殺手細胞（NK 細胞）是一種白血球，它也存在子宮的組織中。過多的自然殺手細胞可能與反覆流產有關，但單純由殺手細胞數量增加或是存在組織內並無法正確預測在之前沒有流產史的女性會不會發生流產^[22]。

與父親共享 HLA

早期研究推論與父親共享人類白細胞抗原（HLA）基因可能會增加流產，但目前仍缺乏有續有力的研究證實^{[來源請求]}。

男性特定的次要組織相容性（minor histocompatibility）

母親對男性特定的次要組織相容性（H-Y）抗原的免疫排斥反應，在許多繼發性反覆流產的病例中具有致病作用。繼發性反覆流產是指在反覆流產發生在成功的活產之後。這個效應的一個例子：在繼發性反覆流產「之前」及「之後」出生孩子的男女比例分別為 1.49 和 0.76^[23]。

免疫因素

1.6.1抗磷脂綜合徵 1.6.2甲狀腺抗體 1.6.3子宮NK細胞增多 1.6.4家長HLA共享 1.6.5男性特定的次要組織相容性

卵巢因素

1.7.1黃體期缺損

感染

慢性子宮內膜炎

評估

治療

流產的心理影響

與晚期疾病的關聯

參考文獻

^ Jeve YB, Davies W. Evidence-based management of recurrent miscarriages. Journal of Human Reproductive Sciences. July 2014, 7 (3): 159–69. PMC 4229790 . PMID 25395740. doi:10.4103/0974-1208.142475.
^ ^2.0 ^2.1 Archived copy. [April 2, 2015]. （原始内容存档于April 3, 2015）.
^ American College of Obstetricians and Gynecologists (ACOG) Repeated Miscarriage FAQ 100 http://www.acog.org/-/media/For-Patients/faq100.pdf?dmc=1&ts=20150820T1255284207
^ ^4.0 ^4.1 ^4.2 ^4.3 Royal College of Obstetricians and Gynaecologists (RCOG). The investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage (PDF). Green-top Guideline No. 17. Royal College of Obstetricians and Gynaecologists (RCOG). April 2011 [2 July 2013]. （原始内容 (PDF)存档于5 July 2013）.
^ The Investigation and Treatment of Couples with Recurrent Miscarriage: Guideline No 17 (PDF). Royal College of Obstetricians and Gynaecologists. （原始内容 (PDF)存档于2013-07-05）.
^ ^6.0 ^6.1 ^6.2 ^6.3 Management of Early Pregnancy Loss. ACOG Practice Bulletin (American College of Obstetricians and Gynecologists（英语：American College of Obstetricians and Gynecologists）). 2001, 24 (February).
^ Hoffman，第181頁.
^ ^8.0 ^8.1 ^8.2 ^8.3 Hoffman，第181–182頁.
^ Ali O, Hakimi I, Chanana A, Habib MA, Guelzim K, Kouach J, et al. [Term pegnancy on septate uterus: report of a case and review of the literature]. The Pan African Medical Journal. 2015, 22: 219. PMC 4760728 . PMID 26955410. doi:10.11604/pamj.2015.22.219.7790.
^ ^10.0 ^10.1 ^10.2 ^10.3 Choices, NHS. Miscarriage - Causes - NHS Choices. www.nhs.uk.
^ 引证错误：没有为名为American College of Obstetricians and 372–9的参考文献提供内容
^ 引证错误：没有为名为:5的参考文献提供内容
^ Branch DW, Gibson M, Silver RM. Clinical practice. Recurrent miscarriage. The New England Journal of Medicine. October 2010, 363 (18): 1740–7. PMID 20979474. doi:10.1056/NEJMcp1005330.
^ Angell RR. Aneuploidy in older women. Higher rates of aneuploidy in oocytes from older women. Human Reproduction. July 1994, 9 (7): 1199–200. PMID 7962415. doi:10.1093/oxfordjournals.humrep.a138675.
^ MacLennan M, Crichton JH, Playfoot CJ, Adams IR. Oocyte development, meiosis and aneuploidy. Seminars in Cell & Developmental Biology. September 2015, 45: 68–76. PMC 4828587 . PMID 26454098. doi:10.1016/j.semcdb.2015.10.005.
^ Rodger MA, Paidas M, McLintock C, Claire M, Middeldorp S, Kahn S, et al. Inherited thrombophilia and pregnancy complications revisited. Obstetrics and Gynecology. August 2008, 112 (2 Pt 1): 320–4. PMID 18669729. doi:10.1097/AOG.0b013e31817e8acc.
^ Nahas R, Saliba W, Elias A, Elias M. The Prevalence of Thrombophilia in Women With Recurrent Fetal Loss and Outcome of Anticoagulation Therapy for the Prevention of Miscarriages. Clinical and Applied Thrombosis/Hemostasis. January 2018, 24 (1): 122–128. PMID 27799457. doi:10.1177/1076029616675967.
^ Williams Z. Inducing tolerance to pregnancy. The New England Journal of Medicine. September 2012, 367 (12): 1159–61. PMC 3644969 . PMID 22992082. doi:10.1056/NEJMcibr1207279.
^ Empson M, Lassere M, Craig J, Scott J. Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant. The Cochrane Database of Systematic Reviews. April 2005, (2): CD002859. PMID 15846641. doi:10.1002/14651858.CD002859.pub2.
^ Patient’s Fact Sheet: Recurrent Pregnancy Lost. American Society for Reproductive Medicine, 8/2008
^ van den Boogaard E, Vissenberg R, Land JA, van Wely M, van der Post JA, Goddijn M, et al. Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review. Human Reproduction Update. 2011, 17 (5): 605–19. PMID 21622978. doi:10.1093/humupd/dmr024.
^ Christiansen O. Recurrent pregnancy loss. Chichester, West Sussex, UK: John Wiley & Sons. 2014: 29–37. ISBN 9781118749180.
^ Nielsen HS. Secondary recurrent miscarriage and H-Y immunity. Human Reproduction Update. 2011, 17 (4): 558–74. PMID 21482560. doi:10.1093/humupd/dmr005.

參考書目

Hoffman, Barbara. Williams gynecology. New York: McGraw-Hill Medical. 2012. ISBN 9780071716727.

外部連結

Frequently Asked Questions About Recurrent Pregnancy Loss

[1] Jeve YB, Davies W. Evidence-based management of recurrent miscarriages. Journal of Human Reproductive Sciences. July 2014, 7 (3): 159–69. PMC 4229790 . PMID 25395740. doi:10.4103/0974-1208.142475.

[asrm.org-2] 2.0 ^2.1 Archived copy. [April 2, 2015]. （原始内容存档于April 3, 2015）.

[3] American College of Obstetricians and Gynecologists (ACOG) Repeated Miscarriage FAQ 100 http://www.acog.org/-/media/For-Patients/faq100.pdf?dmc=1&ts=20150820T1255284207

[RCOG-recurrent-4] 4.0 ^4.1 ^4.2 ^4.3 Royal College of Obstetricians and Gynaecologists (RCOG). The investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage (PDF). Green-top Guideline No. 17. Royal College of Obstetricians and Gynaecologists (RCOG). April 2011 [2 July 2013]. （原始内容 (PDF)存档于5 July 2013）.

[RCOG2003-5] The Investigation and Treatment of Couples with Recurrent Miscarriage: Guideline No 17 (PDF). Royal College of Obstetricians and Gynaecologists. （原始内容 (PDF)存档于2013-07-05）.

[ACOG2001-6] 6.0 ^6.1 ^6.2 ^6.3 Management of Early Pregnancy Loss. ACOG Practice Bulletin (American College of Obstetricians and Gynecologists（英语：American College of Obstetricians and Gynecologists）). 2001, 24 (February).

[FOOTNOTEHoffman181-7] Hoffman，第181頁.

[FOOTNOTEHoffman181–182-8] 8.0 ^8.1 ^8.2 ^8.3 Hoffman，第181–182頁.

[auto7-9] Ali O, Hakimi I, Chanana A, Habib MA, Guelzim K, Kouach J, et al. [Term pegnancy on septate uterus: report of a case and review of the literature]. The Pan African Medical Journal. 2015, 22: 219. PMC 4760728 . PMID 26955410. doi:10.11604/pamj.2015.22.219.7790.

[auto1-10] 10.0 ^10.1 ^10.2 ^10.3 Choices, NHS. Miscarriage - Causes - NHS Choices. www.nhs.uk.

[American_College_of_Obstetricians_and_372–9-11] 引证错误：没有为名为American College of Obstetricians and 372–9的参考文献提供内容

[:5-12] 引证错误：没有为名为:5的参考文献提供内容

[13] Branch DW, Gibson M, Silver RM. Clinical practice. Recurrent miscarriage. The New England Journal of Medicine. October 2010, 363 (18): 1740–7. PMID 20979474. doi:10.1056/NEJMcp1005330.

[14] Angell RR. Aneuploidy in older women. Higher rates of aneuploidy in oocytes from older women. Human Reproduction. July 1994, 9 (7): 1199–200. PMID 7962415. doi:10.1093/oxfordjournals.humrep.a138675.

[15] MacLennan M, Crichton JH, Playfoot CJ, Adams IR. Oocyte development, meiosis and aneuploidy. Seminars in Cell & Developmental Biology. September 2015, 45: 68–76. PMC 4828587 . PMID 26454098. doi:10.1016/j.semcdb.2015.10.005.

[Rodger-16] Rodger MA, Paidas M, McLintock C, Claire M, Middeldorp S, Kahn S, et al. Inherited thrombophilia and pregnancy complications revisited. Obstetrics and Gynecology. August 2008, 112 (2 Pt 1): 320–4. PMID 18669729. doi:10.1097/AOG.0b013e31817e8acc.

[17] Nahas R, Saliba W, Elias A, Elias M. The Prevalence of Thrombophilia in Women With Recurrent Fetal Loss and Outcome of Anticoagulation Therapy for the Prevention of Miscarriages. Clinical and Applied Thrombosis/Hemostasis. January 2018, 24 (1): 122–128. PMID 27799457. doi:10.1177/1076029616675967.

[18] Williams Z. Inducing tolerance to pregnancy. The New England Journal of Medicine. September 2012, 367 (12): 1159–61. PMC 3644969 . PMID 22992082. doi:10.1056/NEJMcibr1207279.

[Empson-CC-19] Empson M, Lassere M, Craig J, Scott J. Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant. The Cochrane Database of Systematic Reviews. April 2005, (2): CD002859. PMID 15846641. doi:10.1002/14651858.CD002859.pub2.

[20] Patient’s Fact Sheet: Recurrent Pregnancy Lost. American Society for Reproductive Medicine, 8/2008

[21] van den Boogaard E, Vissenberg R, Land JA, van Wely M, van der Post JA, Goddijn M, et al. Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review. Human Reproduction Update. 2011, 17 (5): 605–19. PMID 21622978. doi:10.1093/humupd/dmr024.

[22] Christiansen O. Recurrent pregnancy loss. Chichester, West Sussex, UK: John Wiley & Sons. 2014: 29–37. ISBN 9781118749180.

[23] Nielsen HS. Secondary recurrent miscarriage and H-Y immunity. Human Reproduction Update. 2011, 17 (4): 558–74. PMID 21482560. doi:10.1093/humupd/dmr005.

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@@ 第84行： / 第84行： @@
 === 免疫因素 ===
+因免疫因素導致反覆流產的共同特徵是母親對胎兒的{{tsl|en|Immune tolerance in pregnancy|孕期免疫耐受性}}降低<ref>{{cite journal | vauthors = Williams Z | title = Inducing tolerance to pregnancy | journal = The New England Journal of Medicine | volume = 367 | issue = 12 | pages = 1159–61 | date = September 2012 | pmid = 22992082 | pmc = 3644969 | doi = 10.1056/NEJMcibr1207279 }}</ref>。
+====抗磷脂症候群====
+[[抗磷脂症候群]]是一種[[自體免疫疾病]]，是反覆流產的常見原因之一<ref name=RCOG-recurrent>{{cite web|last=Royal College of Obstetricians and Gynaecologists (RCOG)|title=The investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage|url=http://www.rcog.org.uk/files/rcog-corp/GTG17recurrentmiscarriage.pdf|work=Green-top Guideline No. 17|publisher=Royal College of Obstetricians and Gynaecologists (RCOG)|access-date=2 July 2013|date=April 2011|url-status=dead|archive-url=https://web.archive.org/web/20130705172612/http://www.rcog.org.uk/files/rcog-corp/GTG17recurrentmiscarriage.pdf|archive-date=5 July 2013}}</ref><ref name=ACOG2001/>。大約 15％ 反覆流產婦女有高濃度的抗磷脂抗體<ref name=RCOG-recurrent />。在「第一孕期發生兩次或兩次以上流產」或是「第二孕期發生一次或一次以上流產」的婦女，可能需要做血液抗體檢測排除抗磷脂症候群的可能<ref name="RCOG-recurrent"/>。被診斷抗磷脂症候群的婦女在之後的懷孕中通常需要接受[[阿司匹林]]或[[肝素]]的治療，但因為缺乏高品質研究，是否治療仍有爭議<ref name=Empson-CC>{{cite journal | vauthors = Empson M, Lassere M, Craig J, Scott J | title = Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD002859 | date = April 2005 | pmid = 15846641 | doi = 10.1002/14651858.CD002859.pub2 | url = https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0011643/ }}</ref><ref>''Patient’s Fact Sheet: Recurrent Pregnancy Lost''. American Society for Reproductive Medicine, 8/2008</ref>。
+==== 甲狀腺抗體 ====
+[[抗甲狀腺自體抗體]]與反覆流產有關，風險增加（{{link-en|勝算比|odds ratio}}）2.3 倍，95% [[信賴區間]] 1.5–3.5<ref>{{cite journal | vauthors = van den Boogaard E, Vissenberg R, Land JA, van Wely M, van der Post JA, Goddijn M, Bisschop PH | display-authors = 6 | title = Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review | journal = Human Reproduction Update | volume = 17 | issue = 5 | pages = 605–19 | year = 2011 | pmid = 21622978 | pmc =  | doi = 10.1093/humupd/dmr024 }}</ref>。
+==== 子宮內的自然殺手細胞增多 ====
+[[自然殺手細胞]]（NK 細胞）是一種白血球，它也存在子宮的組織中。過多的自然殺手細胞可能與反覆流產有關，但單純由殺手細胞數量增加或是存在組織內並無法正確預測在之前沒有流產史的女性會不會發生流產<ref>{{cite book | last = Christiansen | first = Ole | name-list-format = vanc | title = Recurrent pregnancy loss | publisher = John Wiley & Sons | location = Chichester, West Sussex, UK | year = 2014 |pages=29–37| isbn = 9781118749180 }}</ref>。
+==== 與父親共享 HLA ====
+早期研究推論與父親共享[[人類白細胞抗原]]（HLA）基因可能會增加流產，但目前仍缺乏有續有力的研究證實{{citation needed|date=June 2016}}。
+==== 男性特定的次要組織相容性（minor histocompatibility） ====
+母親對男性特定的次要組織相容性（H-Y）抗原的免疫排斥反應，在許多繼發性反覆流產的病例中具有致病作用。繼發性反覆流產是指在反覆流產發生在成功的活產之後。這個效應的一個例子：在繼發性反覆流產「之前」及「之後」出生孩子的男女比例分別為 1.49 和 0.76<ref>{{cite journal | vauthors = Nielsen HS | title = Secondary recurrent miscarriage and H-Y immunity | journal = Human Reproduction Update | volume = 17 | issue = 4 | pages = 558–74 | year = 2011 | pmid = 21482560 | pmc =  | doi = 10.1093/humupd/dmr005 }}</ref>。
 ===免疫因素===