多次试管失败的姐妹们，去查查免疫吧

nycresident · 发表于 2011-7-6 22:13:16

不好意思，我又去看了看那个医生的博客，低分子肝素（Clexane 或Lovenox）是每天打一针。

nycresident · 发表于 2011-7-12 02:04:27

我把整篇文章都拷下来了
IVF success rates are dependent upon the number of the mature eggs and “competent” embryos available for transfer. A woman undergoing IVF is given fertility drugs for two reasons: (1) to enhance the growth and development of her ovarian follicles in order to produce as many healthy eggs as possible and (2) to control the timing of ovulation so that the eggs can be surgically retrieved before they are ovulated. In cases where the woman has previously received fertility drugs, the subsequent treatment protocol is largely based upon her response to the most recent such treatment regime. If a woman is receiving gonadotropins for the first time, the dosage and regimen is determined by her cycle day (CD) 3 blood FSH antimullerian hormone (AMH), Inhibin-B concentrations, medical history and body type.

Controlled Ovarian Hyperstimulation (COH)

At SIRM, in most cases, the woman begins her cycle of treatment by taking birth control pills (BCP) and having an ultrasound examination to exclude ovarian cysts. The BCP therapy is continued for 10-30 days before initiating daily injections of a Gonadotropin Releasing Hormone agonist (GnRHa) such as leuprolide acetate (Lupron). Both the BCP and Lupron are administered together for an additional two or three days, whereupon the BCP is stopped. The daily Lupron injections are continued until menstruation begins about 3 to7 days after stopping the BCP. By shortening the duration of time on the BCP it is possible to accurately plan the onset of menstruation. In this way we are able to schedule each cycle of IVF to the convenience of the patient and the medical team. Additionally, the combined use of BCP and Lupron reduces the likelihood of Lupron-induced ovarian cyst formation, thereby largely avoiding the need to delay or cancel the cycle of treatment.

As soon as menstruation begins, blood is drawn and if the plasma estradiol (E2) concentration is less than 70 pg/ml, the patient is ready to initiate ovarian stimulation with gonadotropins. If the E2 level is greater than 70 pg/ml, Lupron therapy is continued at the same (or an increased) dosage for a few more days, whereupon the E2 concentration is re-measured. Subsequent failure of the E2 to fall below 70 pg/ml is an indication for a pelvic ultrasound for the detection of an ovarian cyst, the presence of which usually mandates the performance of an ovarian cyst needle aspiration.
Lupron injections are either continued at a reduced daily dosage or (as is now becoming common practice at SIRM), we stop Lupron and switch to low-dose GnRH antagonist (Ganirelix or Cetrotide). On a designated day (usually within a week and a half of the onset of menstruation), a specified regime of gonadotropins (e.g., Gonal F, Follistim, Bravelle, and Repronex) therapy is initiated. Those patients requiring heparin therapy begin this treatment on the first day of receiving gonadotropins.

In a variation on this theme, patients whom have severely diminished ovarian reserve receive intramuscular Estradiol Valerate (E2V) injections (Delestrogen) and/or vaginal estradiol suppositories for a week or longer, prior to and during gonadotropin therapy.

Those patients who have a history of a poor endometrial lining may be prescribed sildenafil (Viagra) vaginal suppositories and oral terbutaline to attempt to improve the uterine lining.
Patients who have activated natural killer cells (NKa) as measured by a K-562 target cell test receive intralipid (IL) therapy by intravenous infusion 7-14 days prior to embryo transfer.
All IVF patients receive oral corticosteroids (dexamethasone or prednisone) daily, commencing with the start of ovarian stimulation and continuing until the first blood beta-hCG test (i.e., pregnancy test). Women who have rising blood hCG levels (a positive blood pregnancy test) 9-11 days after egg retrieval continue taking corticosteroid and heparin (when applicable) beyond the ultrasound confirmation of pregnancy, which is performed at the 6-7 gestational week.

In cases where the blood pregnancy test fails to reveal an appropriate increase in the quantitative beta hCG concentration, heparin therapy is discontinued, and the corticosteroid dosage is slowly reduced over a few weeks and then stopped. Pregnant women continue corticosteroid as well as heparin treatment until the 8th-10th week of pregnancy, whereupon the heparin is abruptly discontinued and the corticosteroid is tapered off over 1-2 weeks and stopped.

Two days after the initiation of gonadotropin injections, the dosage of gonadotropins is substantially reduced, and is then maintained at this lower level until the administration of HCG. Dosage adjustments are sometimes made during the course of the cycle, based upon the patient’s response to medication.

Commencing seven days after the initiation of gonadotropin therapy, the patient undergoes serial ultrasound and plasma estradiol evaluations to monitor her ovarian response. These assessments are aimed at determining the ideal day for administering 10,000 IU of hCG to trigger the final maturation of the egg(s) and the production of progesterone by the ovaries. Lupron or Ganirelix/Cetrotide and gonadotropin injections are discontinued on this day and the patient is scheduled for egg retrieval approximately 35 hours after receiving the intramuscular injection of hCG. Subcutaneous heparin injections are discontinued approximately 12 hours prior to the egg retrieval and re-started after the embryo transfer procedure.

All patients receive an oral antibiotics beginning about seven days after the initiation of gonadotropin therapy and continuing for a few days after the embryo transfer procedure.

Egg Retrieval (ER)
ER involves a non-surgical procedure where, under direct ultrasound guidance, a needle is passed along the side of a vaginal ultrasound probe through the top of the vagina into follicles (small fluid filled spaces that each contain an egg), within the ovary(ies). The follicular fluid is aspirated and collected in a test tube, which is promptly delivered to the embryologist(s) for analysis and processing. The procedure itself is relatively painless, however patients commonly experience some residual postoperative abdominal discomfort and /or cramping that rarely persists for more than a few hours. Postoperatively, all patients are given detailed instructions and are discharged within an hour or two with a prescription for analgesics (pain killers) and other medications as indicated.

Sperm Processing
A sperm specimen is usually obtained from the male partner through masturbation. On some occasions however, physical, medical and/or religious constraints demand that sperm be obtained through condom collection following intercourse, or by inserting a needle directly into the testicle(s) under local anesthesia and aspirating sperm. The two variations of this procedure are known as Testicular Sperm Extraction (TESE) and Percutaneus Epididymal Sperm Aspiration (PESA). TESE and PESA are procedures of choice in cases where there is blockage of the sperm ducts (as occurs following vasectomy or following severe injury or infection), where the man is born without sperm ducts (congenital absence of the vas deferens), or in cases where as a result of testicular failure, sperm does not reach the ejaculatory ducts. Sometimes, in cases of retrograde ejaculation, sperm can be collected from the man's bladder. Infrequently, in men with spinal cord injuries, ejaculation is facilitated by electrical stimulation (electro-ejaculation). Donor sperm, obtained from a sperm bank, can be used when indicated.

Sperm must undergo a biochemical and structural changes known as capacitation, before an egg can be fertilized. Capacitation (which under normal circumstances takes place in the woman's reproductive tract) must be accomplished in the embryology laboratory prior to insemination of the eggs. Motile sperm are processed and activated in specialized culture media and sophisticated techniques are used to enhance poorly mobile sperm.

Fertilization in the Laboratory

Conventional IVF: In vitro fertilization literally means "fertilization in glass". Fluid aspirated from ovarian follicles is examined in the embryology laboratory. The eggs are identified and extracted, and are placed in a specialized culture medium. Several hours later, approximately 50,000-100,000 processed sperm are placed around each of the eggs. The eggs and sperm are allowed to incubate together in a carefully controlled environment. Approximately 16-24 hours later, the eggs are inspected microscopically for fertilization as evidenced by the presence of two nuclear bodies. These binuclear unicellular bodies are referred to as "pro-nuclear embryos".

Intracytoplasmic sperm injection (ICSI): The ICSI procedure involves the direct injection of a single sperm into each egg under direct microscopic vision. The successful performance of ICSI requires a high level of technical expertise. ICSI has literally revolutionized IVF. Initially, ICSI was used specifically to achieve fertilization in male infertility. When ICSI is employed in such cases, the IVF birth rate is unaffected by the presence and severity of the male factor. In fact, even when the absence of sperm in the ejaculate requires that ICSI be performed on sperm obtained through Testicular Sperm Extraction (TESE), the birth rate is no different than when IVF is performed for indications other than male infertility. Today, it is commonly used in conventional (non-male factor) cases. At SIRM, we advocate the use of ICSI in virtually all IVF.

Assisted Hatching: In selected cases where it is felt that the zona pellucida (the envelopment of the embryo/blastocyst) is unusually tough or thickened, a process known as assisted hatching (AH) may be employed. The process involves deliberately making a small aperture in the wall of the embryo (usually with a laser) so as to promote hatching (rupturing) and thereby facilitate implantation. It remains controversial as to whether AH actually improves pregnancy rates.

Selecting the Best Embryos for Transfer

Once embryo division (cleavage) has begun, the embryo will continue to divide at regular intervals. (Embryos that divide the fastest are considered the healthiest and the most likely to implant.) Embryos may be transferred 3 days after fertilization when they are divided to the 6-9 cell stage or as expanded blastocysts, 5-6 days post-fertilization when they comprise 100 or more cells with a small collection of fluid inside). Since embryos that fail to become blastocysts are almost always abnormal and incapable of propagating a healthy baby, it is my personal preference to preferentially advocate that blastocysts rather than cleaved embryos be transferred.

1. Graduated embryo scoring (GES) system: The GES system scores each individual embryo out of a maximum of 100 points. Those embryos that are not transferred to the uterus are subsequently re-examined 2-3 days later to determine whether they have developed into blastocysts. Embryos that on day 3 post fertilization have 6-9 cells and have a GES of >70, are the ones that are most likely to develop into blastocysts. Blastocysts are graded on the basis of their cellularity, differentiation of their outer cellular layer (the trophectoderm), the inner core of aggregated cells (the inner cell mass) and the development of a demonstrable collection of fluid inside the blastocyst (an expanded blastocyst) Blastocysts that contain more cells, have a more expanded blastocele, a more prominent inner cell mass and have a well differentiated trophectoderm have the highest grade and are the ones that are most likely to be “competent” (i.e. likely to propagate a viable pregnancy).

2. Early embryo transfer vs. blastocyst transfer: It has long been recognized that the more advanced the embryo’s state and rate of development, the more likely it is to implant successfully into the uterine lining. It is also well established that “poor quality embryos” tend to divide (cleave) and develop more slowly, and are much more likely to arrest before reaching the blastocyst stage. It is therefore not surprising that researchers would focus on trying to grow embryos to the blastocyst stage in order identify “good quality embryos” that are more likely to implant successfully, by their ability to survive to the blastocyst stage of development.

3. CGH analysis of eggs and embryos: This very promising method of selection, currently in use at the Sher Institutes for Reproductive Medicine (SIRM), allows identification of all chromosomes, providing a much more complete analysis than its commonly used alternative – Fluorescence in Situ Hybridization (FISH). CGH performed on the egg/embryo overcomes the inadequacies of previous methods of embryo selection. A recent SIRM study published in Fertility & Sterility (May, 2007) and another soon to appear in the same journal demonstrates a birth rate of more than 60% per chromosomally normal embryo transferred. Now, for the first time, there is a highly reliable method for differentiating between “competent” and “incompetent” embryos.

With the advent of CGH embryo selection, the goal of “one embryo/one baby” is closer than ever to becoming a reality. CGH-based embryo selection also eliminates the current incentive to transfer multiple embryos at a time in order to improve the chance of success. Embryo selection by CGH holds the potential to decrease the cost per IVF baby and lead to a reduction in overall reproductive health care costs.

Embryo Transfer

Undoubtedly, embryo transfer (ET) is a rate limiting step in IVF. It takes confidence, dexterity, skill and a soft touch to do a good transfer. Of all the procedures in ART, this is inarguably the most difficult to teach. It is a true art and we have seen many women fail to conceive simply because this procedure was not performed optimally.

Shortly before the embryo transfer, the embryos/blastocysts are put together in a single laboratory dish containing growth medium. The laboratory staff informs the clinic coordinator that the embryos are ready for transfer, and the coordinator prepares the patient and informs the physician that a transfer is imminent.

Embryos/blastocysts are transferred to the uterus via a thin Teflon catheter. This procedure is conducted under ultrasound guidance with the woman on her back (in the lithotomy position) and with a full bladder.

Today all embryo transfers should be performed under direct ultrasound guidance to ensure proper placement in the uterine cavity. This practice, properly conducted, will significantly enhance embryo implantation and pregnancy rates. We prefer to perform all embryo transfers when the woman has a full bladder. This facilitates the visualization of the uterus by abdominal ultrasound and causes reflex nervous suppression of uterine contractility. The patient is allowed to empty her bladder 10-15 minutes following the embryo transfer.

It is important that the woman be as relaxed as possible during the embryo transfer because many of the hormones that are released during times of stress, such as adrenaline, can cause the uterus to contract. Accordingly we offer our patients 5mg of oral diazepam (Valium) about a half hour prior to the embryo transfer, to relax them and reduce apprehension.

Some IVF programs believe that imagery helps the woman relax and feel positive about the experience, thereby reducing the stress level. In such a program a counselor and/or clinical coordinator may help the woman focus on visual imagery for a few minutes immediately prior to embryo transfer so as to enhance her relaxation.

The embryo transfer procedure: When the woman is sufficiently relaxed, she is helped into the appropriate position and made as comfortable as possible. (In programs that rely on relaxation therapy, a counselor or nurse is usually present at the patient's bedside, coaching her in relaxation exercises during the procedure.) When the woman is in the proper position, and her bladder is adequately filled, the physician first inserts a speculum into the vagina to expose the cervix and then may clean the cervix with a solution to remove any mucus or other secretions. An abdominal ultrasound transducer is placed suprapubically on the lower abdomen and the uterus is clearly visualized. The physician then informs the embryology laboratory that embryo transfer is imminent and awaits the arrival of the transfer catheter that will be loaded with the embryos.

The physician gently guides the catheter through the woman's cervix into the uterine cavity. When the catheter is in place, the embryologist carefully injects the embryos into the uterus, and the physician slowly withdraws the catheter. The catheter is immediately returned to the laboratory, where it is examined under the microscope to make sure that all the embryos have been deposited. Any residual embryos would be re-incubated, and the transfer process would usually be repeated to transfer the remaining embryos.

The ET procedure is usually painless and takes less than thirty minutes to complete. Sometimes a prior trial embryo transfer (performed on the 8th day of gonadotropin stimulation) points towards potential difficulty in transferring the embryo(s)/blastocyst(s) to the uterus. In such cases, the procedure may be performed with patient under anesthesia.

Transmyometrial Embryo Transfer (TMET): In rare cases where the shape or partial obstruction of the canal leading in to the uterus (i.e. the cervical canal) severely complicates conventional embryo transfer, this method can be used. The patient is first anesthetized, then, using sterile technique, a needle is passed along the side of a transvaginal ultrasound probe through the wall of the uterus, into the uterine cavity. A very thin catheter is then passed through the needle with its tip protruding into the uterine cavity. The needle is partially withdrawn and the blastocyst(s)/embryo(s) are injected. After the embryo transfer, the woman remains immobile for approximately one hour and is thereupon discharged with specific instructions.

Post Embryo Transfer Management

Immediately prior to being discharged following the embryo transfer procedure, an exit interview is conducted, whereby the patient/couple is/are given directions.
Hormonal supplementation usually involves the administration of intramuscular injections of progesterone and/or vaginal suppositories (comprising estradiol valerate and micronized progesterone) until a blood pregnancy test is performed approximately eight days later (the chemical diagnosis of pregnancy). In selected cases, such progesterone treatment can be replaced with Crinone or Endometrin vaginal applications, once or twice daily. If the pregnancy test is negative or the plasma hCG levels fail to rise appropriately in the ensuing days, all hormonal support is abruptly discontinued.

A positive pregnancy test, followed by an appropriate rise in the plasma HCG concentration, is usually an indication to discontinue daily progesterone injections in favor of three times weekly intramuscular injections of hCG 5000 IU, along with daily vaginal estradiol and progesterone suppositories until the 8th week of pregnancy. In patients who experience an exaggerated response to ovarian stimulation with gonadotropins, hCG administration is withheld (for fear of increasing the risk of severe ovarian hyperstimulation), and intramuscular progesterone injections are continued along with vaginal estradiol and progesterone suppositories until the 8th week of pregnancy. Following an appropriate rise in HCG concentrations, the oral corticosteroids are continued until the 10th week of pregnancy. Thereupon, it is tapered down and stopped within a week or two. Heparin injections are continued until the 10th week of pregnancy and thereupon abruptly discontinued.

An ultrasound examination is performed approximately 2-3 weeks after the chemical diagnosis of pregnancy, at which time, designated patients with viable pregnancies, receive a final administration of intralipid (in some cases additional monthly doses of intralipid must be be administered ).

Embryo Cryopreservation (Freezing)

There have been dramatic advances in the technology of freezing and storing human embryos for future use. We cryopreserve (freeze) embryos as blastocysts. The recent introduction of “ultra-rapid freezing” (vitrification) which so rapidly freezes the embryo that it avoids ice formation in the blastomeres has revolutionized embryo freezing. Now, very few chromosomally normal embryos are lost in the freeze/thaw process and pregnancy rates with thawed pre-vitrified blastocysts are hardly different from that reported following the transfer of fresh blastocysts.

nycresident · 发表于 2011-7-12 02:11:58

翻译一下

脂肪乳是移植前7-10天滴注，验血怀孕后再滴注一次。
肝素（每天两针）或低分子肝素（每天一针）是促排第一天开始打，一直打到怀孕8-10周，停针时不需要逐渐减量。如果验血失败当天停针。
强的松或地塞米松是促排第一天开始每天吃，，如果怀孕就继续吃到怀孕8-10周，停药时要慢慢减量，而不是突然停止。如果没怀上就停药。

nycresident · 发表于 2011-7-14 22:25:10

就算是移植了囊胚，也不能保证胚胎没有问题。你只是一次移植失败，说明不了什么问题，没有必要查免疫。但是你如果不放心，医生又愿意给你查，那就去查吧。

nycresident · 发表于 2011-7-17 17:00:13

免疫很复杂，你还是找专门的生殖免疫医生查查。我不是医生，也没有做过免疫治疗，不想耽误你们的治疗。如果当地没有免疫检查，还是去深圳那家医院查查吧。

nycresident · 发表于 2011-7-17 17:03:14

不知国内的免疫5项是查什么，封闭抗体没怀孕的时候一般都是阴的，说明不了问题，要全面检查还是去深圳那家医院。

nycresident · 发表于 2011-8-6 03:39:07

我的甲状腺抗体也偏高，这个是没有办法降的。如果甲状腺素高可以吃药降下来，甲状腺抗体高是免疫出了故障，攻击甲状腺而留下的战绩。如果想知道你是不是生殖免疫有问题，只有查NK毒性高不高了。

nycresident · 发表于 2011-8-6 21:00:09

引用第83楼点球于2011-08-06 19:06发表的回 54楼(nycresident) 的帖子 :2 u( s/ K* O4 W
很感谢你的信息,你是在美国吧?
! @' o9 N& B* S$ U8 r% n. c$ l& M: _6 f1 y" i
多亏了你这个贴的指引,我去看了"等你宝宝"的贴,两周前查了几个抗体,抗心磷脂阴性,类风湿因子性.抗核抗体阳性,ANA 滴度320,斑点型.我看了一下资料,相当于1:320吧.NK指标待查......
+ m4 F/ j% z5 g
# a, d, W5 |$ t1 f( a我三次移植从没着过床,血值没大于过2.胚胎全部是A级,子宫好,内膜好.最近的一次移植前做过宫腔镜和诊刮,J11看见两抹很浅咖啡色分泌物,很开心.不久后开始轮流四肢酸痛,是环绕着关节,肌肉也酸.不仅如此,连左小腹都很酸.J13开始有强烈的刺痛感,断断续续的.上一次移植后J4就开始有刺痛感了,一直持续到J14.
* K7 Z4 J) ]# h0 k0 U.......

脂肪乳是针对nk毒性高的人，不过听你的描述，你可能还有TNF高的问题，TNF高靠脂肪乳是压不下来的。建议你还是去深圳看看吧，只有那家医院治疗方案齐全。

nycresident · 发表于 2011-8-7 07:06:56

你可以打电话到Beer中心问问，他们接受远程病人，你可以把血样放在冷冻箱里速递过去。
http://repro-med.net/repro-med-s ... ;id=1&Itemid=14

reproductive immulogy 方面的检验，很多诊所是做不了的。美国也就是有4家实验室可以做，英国有一家，欧洲别的国家还没有听说可以做。

英国你方便去吗，这个医生好像不错
Dr. Paul Armstrong
Dr Paul Armstrong
The Portland Hospital
205-209 Great Portland street
London W1W 5AH England
0207-580-4400 (Speak to Paulette his secretary)
0207-390-8156 (Speak to Milly his secretary)
Email: drpaul.armstrong@btconnect.com
- OR -
Royal London Hospital
Whitechapel London E1 1BB England
ph 0207-377-7000 ex 2579
Ph (Speak to Anne, his secretary) 171-377-7000 ext. 2579
URL: www.drpaularmstrong.co.uk
Patient comments: “Does both LIT and IVIG. LIT is done subcutaneously and intravenously. He states it is more effective and works faster this way when I asked him. He also wanted me to do the LIT just the once 3 weeks before ET, so no
retesting.” “Does not do donor LIT. He only meets patients on Fridays and does LIT treatments on Tuesdays. Dr Armstrong does advocate IV LIT along with subQ.”
Also: “As of January 2009, apparently he will prescribe Intralipids”

另外，你可以到yahoo去注册一个id，然后申请加入这个discussion group http://health.groups.yahoo.com/group/immunologysupport/，里面有很多信息，你到file那里去可以下载一些有用的文件。

nycresident · 发表于 2011-8-8 07:10:07

NK毒性是指K562 target cell test或NK assey。普通实验室查NK细胞数量，合格标准和免疫不孕实验室的标准不一样的，所以人家如果给你的结果是好的，还是不能说明你没有问题。TNF-a是Tumor necrosis factor-alpha，肿瘤坏死因子，查TH1:TH2 Intracellular Cytokine Ratio就行。
。

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