这是从SIRM转来的免疫治疗篇
A）皮质类固醇 （泼尼松，泼尼松和地塞米松）
类固醇已经是IVF的常规疗法。我们通常在促排前10天让病人每天吃地塞米松，一直吃到抽血验孕那天。如果确诊怀孕，还要继续吃到满12周。如果没怀孕就停吃药。
B）肝素
大量事实表明，皮下注射肝素可以大大改善IVF活胎出生率。对APA呈阳性，NK活性没超标的病人，每天注射5000U两次。取卵那天开始暂停打肝素，直到移植时又重新开始打。血小板不正常的病人不能打。
D）静脉滴注免疫球蛋白
免疫球蛋白是一种血液制品，它可以抑制激活了的NK细胞，它也可以减少CTL（激活了的T细胞）的活动力，CTL会产生TH1细胞因子，是损伤早期着床胚胎祸首。
免疫球蛋白可以抑制另一种白细胞-T细胞。当T细胞不适当激活时，会产生一种自身抗体，如抗磷脂抗体（APA）或抗甲状腺抗体（ATA）。
免疫球蛋白含有一种抗独特型抗体，可以直接抵疫很多自身抗体（自身抗体攻击自身的细胞）造成的损伤。
病人在移植前7-14天滴注40g的免疫球蛋白，14天验血怀孕时再打一针40g。
E）脂肪乳剂Intralipi（英特利匹特）
脂肪乳剂含10%大豆油，1.2%蛋黄，2.25%甘油，对人体无害，价格也便宜。对于NK活性过高的治疗，我们从2007年底开始用长链脂肪乳剂代替免疫球蛋白，50%的病人打了长链脂肪乳剂后成功怀孕，效果不比免疫球蛋白差。用法是移植前7-14天打一瓶100ml 的 20%intralipid，14天验血怀孕时再打一瓶。
THERAPEUTIC IMMUNOMODULATION
a. Corticosteroid Therapy (Prednisone, Prednisolone and Dexamethasone). Steroid therapy is routine in most IVF programs. Some advocates use daily oral methyl prednisolone. We prescribe oral dexamethasone commencing about ten days prior to initiating ovarian stimulation with gonadotropins, and continuing until the diagnosis of pregnancy. In the event of a negative test (Beta HCG or ultrasound), the dosage is tapered over a period of seven to ten days, and then discontinued. Pregnant patients often continue treatment through the first trimester. Steroids are believed to act by inhibiting the cellular immune response.
b. Heparin. There is compelling evidence that the subcutaneous administration of heparin (at a dosage of 5000 units twice daily to women undergoing IVF for female causes of infertility who test positive for APAs, but negative for NK activation, significantly improves IVF birth rates. Heparin administration is withheld on the day of egg retrieval until immediately following embryo transfer, whereupon it is recommenced and continued until the 8th week of pregnancy. Heparin is thought to act by repelling APAs from the surface of the trophoblast (the early "root system" of the embryo). Provided that platelet counts are normal, are checked on a regular basis, and heparin is withheld on the day of egg retrieval, its administration is virtually risk-free.
c. Low Molecular Weight Heparin (LMWH) (Lovenox, Clexane, and Fragmin). LMWH is equally as effective as heparin. It has the added advantage of having to be administered just once (rather than twice) daily and it causes less local irritation or bruising. It does cost considerably more than regular heparin, but is preferred by many patients in need of this therapy.
d. Intravenous Immunoglobulin G (IVIg). IVIg is a sterile protein preparation derived from human blood. Every effort has been made to ensure that it is free of bacterial and viral contamination. There are basically four ways in which IVIg is believed to offset or counter the anti-implantation effects associated with reproductive immunologic deficiencies.
First, it is a potent suppressor of activated (toxic) Natural Killer cells (NKa)-the immunologic guardians of the uterus.
Second, IVIg reduces the activity of CTL's (activated T-cells). This is another type of immunologic cell that acts by producing TH-1 cytokines ("toxins") that can damage the early implanting conceptus.
Third, IVIg is believed to suppress the ability of another type of immune cell called B cells. When activated abnormally, these cells produce damaging autoantibodies such as antiphospholipid antibodies (APAs) and antithyroid antibodies (ATAs).
Fourth, IVIg contains anti-idiotype antibodies that directly counter many of the damaging effects of autoantibodies (antibodies that attack the body's own cells), such as APAs, thereby protecting the early "root system" of the embryo/conceptus from damage.
IVIg has had some undeserved bad press. Since it is a blood derivative, the thought of administering it in an era where HIV is rampant, is frightening to most. However, consider the following: IVIg products available in the United States and the United Kingdom are subject to the most stringent controls and scrutiny. According to the manufacturers of IVIg, there has not been a single case of HIV viral transmission in more than two million administrations and there have only been a few isolated cases of Hepatitis C. This is not surprising, since IVIg is derived from the very same blood pool used for transfusion purposes, and since millions of units of blood have been administered in the United States over the last 7 years without any reports of HIV transmission.
The IVIg available in the U.S is thoroughly tested. We hold that if administered properly by qualified medical personnel, and if the appropriate precautions are taken, IVIg currently used in this country is virtually devoid of viral contamination.
We recommend that IVIg for increased NKa be administered 7-14 days prior to embryo/blastocyst transfer. The selective use of immunotherapy has, on numerous occasions, enabled us to achieve successful pregnancy in patients who had previously suffered repeated IVF failures (4 or more). Many such patients had previously been advised not to try again with their own eggs. We are able to report IVF births occurring with the aid of IVIg in numerous cases where the woman had previously experienced more than ten IVF failures. I recall a case where a 42 year old woman was successful with us (using her own eggs) following 22 consecutive prior IVF failures. We believe that such results could not have been achieved without access to selective immunomodulation.
In cases of autoimmune immunologic implantation dysfunction associated with NKa+ we recommend giving 40G IVIG slowly, 7-14 days prior to embryo transfer (ET) and then repeating the dosage once more soon after a positive beta hCG result, 11 and 13 days post egg retrieval (ER). For alloimmune implantation dysfunction, we treat with 60G of IVIG 7-14 days prior to ET. This is repeated with the positive, 2nd beta and thereupon, 60G every month or 30G given every 2 weeks until the 24th week of pregnancy. Severe side effects of IVIg treatment are rare. Patients may suffer from malaise, fever and headache. IVIg is a relatively expensive mode of treatment - the cost for one course of treatment being $3,500-$5,500, thus preventing more wide use of this preparation in IVF
Indeed, some NKa+ women do conceive and then continue with healthy pregnancies, without having undergone prior immunomodulation therapy with IVIg (or intralipid). However, in our opinion, the chance of this occurring is so significantly reduced as to justify the recommendation that such treatment be administered in all cases where a woman undergoing IVF tests positive for NKa (NKa+) and in all cases of alloimmune implantation dysfunction (regardless of her NK status). Presently, there are fewer than a half dozen highly specialized Reproductive Immunology Reference Laboratories in the United States that are capable of measuring the necessary immunologic parameters with a sufficient degree of sensitivity and specificity to be clinically useful. We do not regard measurement of factors such as lupus anticoagulant to be of practical value in the diagnosis and management of immunologic implantation dysfunction.
e. Intralipid, a possible replacement for IVIG. For us at SIRM, advocating the use of IVIG over the last decade has come at a considerable price. Clearly, women requiring IVIG have been concerned about the cost (more than $4000 per dosage), reported side effects and, given the HIV/hepatitis scare, have been reluctant to receive a blood product. To make matters worse, under-informed critics have for unexplained reasons played on such unfounded fear often raising it to the level of alarm. The fact is that over the years we have administered IVIG to thousands of women, without a single report of viral transmission and few significant (but always transient) side effects.
In 2006/2007, reports began to surface regarding a low cost (about 1/10 the cost of IVIG) synthetic product called Intralipid, which upon being infused more than a week prior to embryo transfer would lower NKa and furthermore, was virtually free of side effects. Intralipid stimulates the immune system. Evidence from both animal and human studies suggest that intralipid administered intravenously may enhance implantation and maintenance of pregnancy. Intralipid is a 10% intravenous fat emulsion used routinely as a source of fat and calories for medical patients who require intravenous feeding. It is composed of 10% soybean oil, 1.2% egg yolk phospholipids, 2.25% gylcerine and water. The appeal of Intralipid lies in the fact that it is relatively inexpensive and is not a blood product.
In late 2007, we began evaluating the effect of Intralipid in patients who had activated Natural Killer cells, and for whom IVIG therapy would otherwise be indicated. Thus far, we have treated numerous women with NKa using Intralipid 20%. More than 50% of the patients achieved viable ongoing pregnancies, showing Intralipid therapy to be at least as effective (and perhaps even more so) than IVIG. There were no significant side effects and patient tolerance of this treatment was high. Against this background, we at SIRM have elected to offer intralipid therapy as a low cost, safe and effective alternative to IVIG therapy for both alloimmune and autoimmune implantation dysfunction. 100ml of solution 20% in 500cc of normal saline solution is infused intravenously 7-14 days prior to ET, immediately following blood diagnosis of pregnancy (beta-hCG test) and then monthly until the 20th week of pregnancy.
[ 此帖被nycresident在2010-12-10 23:51重新编辑 ]
