美国生殖专家与病人的问答

nycresident

自从我考虑赠卵试管，就一直到各大论坛搜罗资料，闯入这个专家问答网，学来很多东西。我会时不时把姐妹们关心的对答贴出来，加上翻译。
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http://forums.haveababy.com/lofiversion/index.php?f4.html
http://forums.haveababy.com/lofiversion/index.php?f10.html

nycresident

病人 Maggie：
) N( k! N) s7 F$ B% J% SI'm currently taking .25mcg levothyroxine daily. My last TSH reading was right before IVF cycle at 2.94. Today I'm 8dp3dt and

HCG=13
FT4=1.26 lab range .89 - 1.8
% u! e  D) f, F3 t: |TSH=4.08 lab range .24 - 4.2

5 L6 b) q6 e/ NDo I need to get my levothyroxine dosage increased immediately? Or is it not a big concern?
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This is the 1st time after 2 yrs of infertility treatment that we have gotten a positive beta. This is also the 1st cycle I have been on levothyroxine.
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# {0 t" K# `3 u$ X0 {$ _+ A# BThanks!
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( d! G# n# d& G2 g专家 Geoffrey Sher, MD：
5 C) D9 I. W) g* W+ S- sAbout 50% of women who have autoantibodies to their own thyroid tissues (antithyroglobulin and/or antimicrosomal antibodies) regardless of whether or not there are clinical signs or symptoms of reduced thyroid hormone activity (hypothyroidism) have activated Natural Killer cells (NKa+ and/or activated T-cells in their blood. Such women often present with reproductive failure manifesting as infertility, recurrent IUI and IVF failure or repeated pregnancy loss. The antithyroid antibodies (antimicrosomal and/or antithyroglobulin antibodies) do not cause the problem. They act as markers pointing to an underlying immunologic implantation problem that occurs when NKa or T-cell activation is present. . Here, as soon as the embryo starts to burrow into the uterine wall, "toxins" are produced (locally) that impair implantation. In some cases, the pregnancy is lost before a blood test can detect it, while in other cases a miscarriage occurs. [Some pregnancies escape the "toxic gauntlet" and proceed.
One of the most significant hints that a non symptomatic woman might have antithyroid antibodies is a family history of hypothyroidism (under performance of the thyroid gland requiring thyroid hormone therapy).
8 P2 K/ j: s" h  ~' a- U3 hWe were among the first to demonstrate that women who have reproductive failure associated with antithyroid antibodies and NKa+/T-cell activation can have successful IVF outcomes following administration of intravenous gammaglobulin (IVIG) . Women who are antithyroid antibody positive who do NOT have NKa+ and or T-cell activation do not require or benefit from IVIG therapy.
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/ j  v, C& S5 G+ y+ XMight I recommend that you call Patricia Barton (Patient Relations) at (800) 780-7437 or 702-699-7437 at SIRM-Mosaic and ask her to arrange for an in-person consultation at my New York or n Las Vegas office . Alternatively, you could ask her to set up a free medical telephone consultation with me.

SIRM offers qualifying couples access to the Outcome Based Plan (OBP). Participants are eligible for a refund of up to 100% of our in-house medical service-related fees, if the egg retrieval and subsequent transfer of all (fresh/frozen) embryos (over a period of months) does not result in the birth of a baby. Patients can re-qualify for the OBP up to 3 times.
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You might be interested to know that the 3rd edition of my book "In Vitro Fertilization the A.R.T of Making Babies” was recently released and is available at most bookstores as well as from www.amazon.com. It is very comprehensive, current and covers the entire spectrum of the ART arena.
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Geoff Sher

nycresident

甲状腺病人问：我现在正每天服用.25mcg levothyroxine ，试管前TSH是2.94，在正常范围内，移植8天后验血TSH=4.08（正常范围0.24~4.2），我要不要增加levothyroxine的量。
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医生答：50%的甲状腺球蛋白抗体和抗甲状腺微粒抗体阳性的妇女自然杀伤细胞活力（NK细胞活力或T细胞活力）都高于正常，不管这些人有没有甲状腺症状。这些妇女往往会有怀孕失败的风险，因为子宫激活了的NK细胞和T细胞会分泌有毒物质，侵蚀胚胎的根基，使其不能在子宫里着床或发育。如果家族有甲减病史的人尽管自己没有症状，也要去查查NK或T细胞活力高不高。
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我们诊所的成功经验是通过静脉注射免疫球蛋白抵御这些细胞的影响。如果甲状腺球蛋白抗体和抗甲状腺微粒抗体阳性但NK和T细胞没有激活的患者不需要免疫球蛋白的治疗。

nycresident

你的情况可能和甲减关系很大，甲减患者容易流产的。但没听说甲减会影响受精卵质量。你有做过免疫方面的检查吗？北京大学第三医院可以做呀。如果查出来是NK或T细胞问题，可以试试免疫球蛋白，或intralipids。SIRM诊所已经试用intralipids 2-3年了，主要是对需要免疫球蛋白治疗单又不够钱、或反对使用血清制品的患者，效果还不错。

如果查出来是免疫的问题，可以再最后试一次试管？还有，如果你的免疫问题不解决，光借卵也没有用的。如果你的卵子也不行了，那只有借卵借房了。

nycresident

不是。打封闭抗体是从lg那里抽血，制成血清蛋白，再打到你手臂上，就跟小时候大疫苗针一样。免疫球蛋白，是要从静脉点滴，需好几个小时。免疫球蛋白很贵的，打一次要4000-6000元。

nycresident

levothyroxine是左甲状腺素钠，是一种调节甲状腺荷尔蒙的激素。但是医生说了，甲状腺荷尔蒙不是问题的根本，而是有这种病的人免疫系统一直处于高度警备状态，一有风吹草动就放出NK细胞，所以就算吃药把TSH降到正常，还是会有问题的。有些人移植前检查NK细胞正常，但移植后NK细胞就激活。所以有这个病而且有过多次怀孕失败的人，移植后需要隔段就验一次血，看看NK是不是活力过高，医生好根据检查结果调整药量。

nycresident

intralipids是合成剂，不是血液制品。国内叫脂肪乳剂。
http://www.poptool.net/health/dir_wdrug/1511/drug_280.html

nycresident

再拷来一篇RIA实验室关于抗甲状腺抗体对怀孕早期失败影响的文章

# s. h9 S- A" M# n/ s) wAntithyroid Antibodies
In 1990, Stagnaro-Green demonstrated in a prospective analysis that thyroid antibodies were markers for "at-risk" pregnancies. The two antibodies studied, anti-thyroid peroxidase and anti-thyroglobulin antibodies, are collectively referred to as anti-thyroid antibodies (ATA). Many reports have since corroborated the markedly increased prevalence of ATA in women who experience reproductive failure, especially first trimester miscarriages. Pratt, et. al., showed that 67% of women with recurrent first trimester losses had ATA, compared to 17% of controls. None of the participants in either group had clinical manifestations of thyroid disease.

Although there is a highly positive correlation between the presence of ATA and fetal loss, no definitive pathophysiology has been identified. Several hypotheses have been proposed to explain this phenomenon. One hypothesis states that these patients have very mild hypothyroidism. Studies to date fail to indicate low thyroid hormone levels in those who miscarried. Proponents suggest that serum hormone levels do not necessarily reflect thyroid dysfunction.

Another opinion is that ATA are markers for predisposition to autoimmune disease, and that the latter is what actually causes the miscarriage. Notable is that ATA is present in up to 45% of patients with systemic lupus erythematosus (SLE). In another study, 70.8% of patients with recurrent spontaneous abortion (RSA) had various autoantibodies, leading the authors to conclude that some patients with unexplained infertility and RSA suffer from polyclonal B-cell activation.
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Antithyroid antibodies appear to be markers for abnormal T-lymphocyte function. Significant increases in the endometrial T-cell population and the cytokine interferon gamma have been observed in infertile women with ATA. It can be presumed that infertile patients who demonstrate ATA can be classified as having the reproductive autoimmune failure syndrome (RAFS).
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Patients with RAFS should have immune evaluations that include blocking antibodies, ANA and APA panels, NK cell number and activity, DQ alpha genotyping, and gene mutations leading to inherited thrombophilias.
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- A4 t4 T( r* X, S+ v! D1 mTreatment for Antithyroid Antibodies
; N; o) \% k. M# a/ G. b: TIn IVF patients, antithyroid antibodies (ATAs) are treated with intravenous immune globulin (IVIg) before the IVF transfer. There is no specific treatment for ATA in patients with recurrent miscarriage unless it is associated with other abnormalities.

nycresident

宝宝快点来，你的问题应该是卵子质量问题。免疫不孕是在受精卵质量很好、子宫环境都不错的前提下，而成反复几次都不着床才会考虑的。
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3 j0 Y9 J  u4 p7 a2 F) l) \9 Y并不是所以抗甲状腺抗体高的患者NK细胞或T细胞都被激活了，但如果你这方面得抗体高，应该查查NK和T细胞活力。

nycresident

文章大意上说
& f4 e2 S* S* z) S% u$ E9 n1990年Stagnaro-Green做的研究发现习惯性流产是和抗甲状腺抗体有关联的。
其中一种假设是ATA抗体作为信标早已预先储存在自身免疫系统中，ATA的出现，向自身免疫系统就警示疾病已经入侵了，自身免疫系统的一系列措施才是流产的真正原因，而不是ATA本身。

+ M8 X; K. @& ]  N7 ]+ z+ J值得注意的是，45%的SLE（红斑性狼疮）的患者也有ATA抗体。在另一组研究中也发现，70.8%原发习惯性流产的妇女都有各种各样的自身抗体，使笔者相信不明原因不孕和习惯性流产的罪魁祸首是多克隆B细胞的激活。

, m" D5 I( c4 T很明显，ATA抗体是不正常T淋巴细胞的信标，我们发现在有ATA抗体的不孕妇女身上发现大量的T细胞群和细胞因子干扰素。可以说，ATA阳性的不孕患者可以归类为自身免疫生殖失败症（RAFS）。

有RAFS的病人应做免疫方面的检查，包括封闭抗体，抗核抗体ANA，抗血小板抗体APA，NK细胞数量和活力，人类白细胞抗原-DQ，基因突变引起的遗传性血栓倾向。
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, V3 F6 t+ ]4 {9 T5 o7 e1 e抗甲状腺抗体的治疗：
2 e; u+ s: |0 |0 {+ t5 e# ~  w对有抗甲状腺抗体的IVF病人治疗的方法是，在移植前做免疫球蛋白静脉滴注。