http://haveababy.com/fertility-information/ivf-authority/my-ivf-cycle-failed-what-went-wrong_19-2/

However, it is incorrect to assume that all embryos reaching the blastocyst stage are euploid (“competent”). It is true that many aneuploid embryos are lost during development, and that those that survive to the blastocyst stage are far more likely to be competent than are earlier (cleaved) embryos.

.

During the normal ovulation cycle, ovarian hormonal changes are regulated to avoid irregularities in production and interaction that could adversely influence follicle development and egg quality. As an example, small amounts of androgens (male hormones such as testosterone) are produced by the tissue surrounding the ovarian follicles (stroma) during the pre-ovulatory phase of the cycle to enhance late follicle development, estrogen production by the granulosa cells (that line the inner walls of follicles), and egg maturation.

..

http://haveababy.com/fertility-information/ivf-authority/my-ivf-cycle-failed-what-went-wrong-12/

What we now do know for certain is that cleaved embryos (day 2-4, post-fertilization) that fail to develop into blastocysts are with few exceptions aneuploid or “incompetent embryos.”. So if these cleaved embryos had been transferred, they almost certainly would not have developed into blastocysts, and would not have propagated a pregnancy anyway. Thus, there would have been no benefit to transferring them earlier. In my experience, there is no validity to the often quoted assertion that an embryo would develop better and have a greater chance of propagating a baby by being inside the uterus earlier, than it would by being allowed to first develop into a blastocyst in an incubator.

.

Indeed, were it possible to determine with confidence, through microscopic grading, which embryos would develop into blastocysts and which would not, then it would not matter whether those embryos were transferred sooner or later. What we do know is that cleaved, day-3 embryos that are found through CGH testing/ karyotyping to have a full quota of 46 chromosomes (i.e. are euploid) will, in about 90% of cases, develop into expanded blastocysts (regardless of the age of the egg provider).

By comparison, untested embryos (where it is not known whether the embryo is aneuploid or euploid) have but a fraction of the chance (at best 40%) of developing into blastocysts. While chromosomal integrity of the embryo is not the sole determinant of “competency” (epigenetic and metabolomic factors also play a role), it is by far the most important variable.

.

http://haveababy.com/fertility-innovations/the-evolution-of-cgh-egg-and-embryo-testing-at-sirmreprocure/

This study showed that the transfer of 1-2 embryos/blastocysts derived from CGH-normal eggs (mean=1.7 per woman), resulted in live births >70% of the time ( i.e. > double the national average).  In the process, the risk of multiple pregnancies was markedly lower, and chromosomal miscarriages and birth defects were drastically reduced.

.

The process of splitting the cycle in two ; i.e. performing CGH on the first polar body of the egg or on a blastomere taken from a day 3 embryo, allowing the embryos to go to blastocyst, cryobanking these, and deferring the embryo transfer to another time, is referred to as Staggered -IVF (St-IVF).

.

http://haveababy.com/fertility-innovations/immunologic-treatment/

Intralipid (IL), is a synthetic product composed of 10% soybean oil, 1,2% egg yolk phospholipids, 2.25% glycerin and water. Based on research performed at SIRM and elsewhere, infusion of IL lowers Natural Killer cell activation (Nka) as effectively as does, intravenous gammaglobulin (IVIG.) When indicated IL (as with IVIG) is infused 7-10 days prior to ET and one more time again after a positive pregnancy in women whose Nka is due to an autoimmune causes (antiphospholipid antibodies and/or antithyroid antibodies). In cases of alloimmune implantation dysfunction (DQa and/ HLA matching between the embryo recipient and the male partner) the same applies but in this situation the infusion is repeated at 2-4 week intervals until the 24th week of pregnancy.
We have supplanted IVIG with IL therapy in a significant number of women undergoing IVF , and who had immunologic embryo implantation dysfunction. The results thus far have been excellent, way beyond our initial expectations.
At last we now have a safe and inexpensive alternative to IVIG therapy…Intralipid! What is more, IL costs about 10 times less than IVIG, is not a blood product and is without significant side effects.

.

http://haveababy.com/fertility-information/ivf-authority/the-future-of-ivf-frozen-embryo-transfer-with-cgh-tested-single-blastocyst/

CGH Embryo Selection
Against this background, intensive research has focused on identifying and then preferentially transferring “competent” embryos. About 7 years ago, we at SIRM became the first to introduce genetic testing of embryos through comparative genomic hybridization (CGH) into the clinical IVF arena. CGH testing, for the first time permitted recognition of all 46 chromosomes in the embryo’s cells. We now know that an embryo that has all 46 chromosomes intact will, provided that it is transferred into a receptive uterus (free of anatomical or immunologic impediments) with produce a viable pregnancy 60-70% of the time. Proudly, we have since been responsible for the births of hundreds of babies following the transfer of such CGH-normal embryos.

.

Solche SS Raten mag ich gern! Leider wird es die Untersuchung hier wohl nicht geben. Muss ich mal meine KiWu fragen.

..

http://haveababy.com/fertility-information/ivf-authority/eggembryo-quality-critical/

Up until a woman reaches her mid thirties, only about 2 in 5 of her eggs will likely be chromosomally normal. As she ages beyond her mid-thirties there will be a a progressive decline in egg quality such that by age 40 years only about 15%-20% of eggs are euploid and, by the time the woman reaches her mid-forties, less than 10% of her eggs are likely to be chromosomally normal. While most aneuploid embryos do appear to be microscopically abnormal under the light microscope, this is not invariably so. In fact, many aneuploid embryos a have a perfectly normal appearance under the microscope. This is why it is not possible to reliably differentiate between competent and incompetent embryos on the basis of their Microscopic Grade alone.

.

Mist, 2 von 5 Eizellen sind eh schon zum Sterben verurteilt, einfach wegen dem Alter. Glaube beim naechsten Mal gibts bei uns einen Blasto-TF! Und selbst wenn sie unter dem Mikroskop schoen aussehen, heisst das nicht, dass sie auch wirklich gut sind. 😦

..

http://haveababy.com/fertility-innovations/staggered-in-vitro-fertilization/

First, it significantly increases the success rate per embryo transferred and thereby allows fewer embryos to be transferred per ET. This reduces the incidence of multiple births. Second, by reducing the risk of aneuploidy, the commonest cause of early pregnancy loss, it significantly lowers the incidence of miscarriages. Third, it minimizes the risk of chromosomal birth defects such as Down’s syndrome.

.

Also da muesste man ja warten, bis di genetischen `Ergebnisse da sin, ob alle 46 Chromosomen da sind. 😦 Und ich denke, dass in D das auch nicht bezahlt wird…

..

http://haveababy.com/fertility-information/ivf-authority/array-cgh-vs-metaphase-cgh-in-ivf-which/

Besser wenn man Vitrifikation nutzt, um die EZ einzufrieren, weil es weniger Verluste gibt dabei (<10% vs xx?%)

..

http://haveababy.com/fertility-information/ivf-authority/ovarian-stimulation-what-high-responders-and-poor-responders-have-in-common/

About 4 months in advance of an ovulation cycle, a batch of eggs is recruited to be used several months later. What happens during this long “recruitment journey” is one of the mysteries of reproductive medicine, remaining a poorly understood biological event. Egg recruitment is however an inevitable prelude to eggs developing and ultimately reaching “starting gates” of the cycle in which they are to be used.  At that point, they are contained in small fluid filled spaces, referred to as “antral follicles.” The subsequent development of these antral follicles into larger functional follicles is under the influence of follicle stimulating hormone (FSH).

.

4 Monate _vor_ einer Eireifung faengt das Ei schon an sich zu entwickeln. 😮 Sprich wenn vor 4 Monaten etwas war, kann man schlechte Eier haben. *ohnmacht* Warum sagt das einem keiner>>>

..

http://haveababy.com/fertility-information/ivf-authority/understanding-immunologic-implantation/

Immunologic acceptance of the implanting embryo by the uterus of the mother is both highly complex and magnificent. Not only is it essential for pregnancy to occur, but it also sets the scene for our body’s own cells, tissues and organs to be shielded from attack by our own immune systems. For a moment, consider how, when confrontedby foreign proteins (bacteria, viruses, foreign tissue grafts/transplantation), the body’s immune system goes on the attack, but yet an embryo that is derived from proteins that come from another individual (the sperm or paternal antigen), usually safely implants in the pre-pregnancy uterine lining and then grows into a healthy baby.This phenomenon has come to be referred to as the “immunologic riddle” of pregnancy.

.

It is well known that the reason the implanting normal embryo thrives in the womb is that unique immunologic adjustments convert the pre-pregnancy uterine lining (decidua) into a “privileged site” where the embryo and the fetus come to be regarded as the “body’s own” and as such are protected from immune attack. This initial acceptance of the embryo as “self” or “friend” rather than “non-self” or “foe” (in spite of it being composed partially of the father’s “foreign” cells), is one of the miraculous adaptations of nature, and is in large part responsible for our survival as a species.

As soon as implantation begins, the paternal genetic contribution to the embryo (so called DQ alpha genes) initiates asignal to the pre-pregnancy decidual immune system which thereupon determines whether the embryonic “allograft” should be welcomed as “friend” or be rejected as “foe” through immune attack. The process is referred to as “alloimmune recognition.”Given that with the exception of monozygotic twins, interpersonal differences in genotype are inevitable, it follows that maternal and paternal DQ alpha gene combinations will usually also differ in the vast majority of cases. Thus, preservation of the human species required that in spite of such immunogenetic dissimilarities, the immune system of the pre-pregnancy endometrium (decidua) evolutionarily adapt and recognize the embryo as friend rather than foe.

.

There are 3 varieties of cytokines, two of which play defining roles in the maintenance of implantation:The first is TH-2 cytokines, which encourage growth and expansion of the trophoblast and promote proliferation of blood vessels (angiogenesis). TH-1 cytokines promote destruction (cytolysis) of trophoblastic cells and also cause blood to clot (procoagulant effect).A balance between TH-1 and TH-2 cytokines is essential for normal implantation and development of the placenta (placentation). Over-activity (dominance) of TH-1, the hallmark of NK cell and CTL activation, leads to damage of the trophoblast, implantation dysfunction and reproductive failure.

.

http://haveababy.com/fertility-information/ivf-authority/understanding-immunologic-implantation_16-2/

With paternal-maternal DQ alpha matching, it often takes several pregnancies for natural killer cell activation to build to the point that a woman with alloimmune implantation dysfunction will present with clinical evidence of implantation dysfunction. Sometimes it starts off with one or two pregnancies surviving to the birth of a baby, whereupon NK cell activity later starts to build, leading to one or more subsequent early miscarriages. Eventually the NK cell/CTL activity is so high that subsequent pregnancies can be lost before the woman is even aware that she was pregnant at all. At this point she is often diagnosed with secondary “unexplained” infertility.

.

There are also certain reproductive diseases such as endometriosis, where cell membrane phospholipids are often altered by the disease process, and then combine with proteins to evoke the production of so called antiphospholipid antibodies (APAs)Certain types of APAs can both directlydamage the trophoblast and can also lead to a reduction of Treg lymphocytes, culminating in activation of NK/CTLs.

.

In the United States, effective treatment of NK/CTL activation associated with either alloimmune or autoimmune implantation dysfunction requires the administration of Intralipid or IVIG. Such treatment is usually much more likely to be successful in the case of autoimmune implantation dysfunction where the NK/CTL activation is present in advance of the uterus being exposed to the embryo. It is not nearly as effective for the treatment of alloimmune implantation dysfunction where a DQ alpha matching embryo will exert a sustained activation of NK/CTLs over several months of gestation.

.

sprich IVIG oder IL hilft bei Immunbedingten Fehlversuchen aber NICHT bei HLA Sharing!

IVIG/IL therapy should preferably always be administered in combination with corticosteroids at an adequate dosage, starting 7-14 days prior to planned embryo transfer. With alloimmune implantation dysfunction shuch treatment should be repeated every 2-4 weeks through the 1st half of pregnancy. The goal is to down-regulate NK /CTL activation and thereby reinstate a TH-1: TH-2 cytokine balance in advance of a “competent” non- DQ alpha matching embryo reaching the uterus. When it comes to autoimmune implantation dysfunction Intralipid and/or IVIG (with corticosteroids) need only be administered twice; (once, 7-14 days prior to embryo transfer, and the second administratio should be given when the beta hCG blood level has shown evidence of an appropriate rise, thereby suggesting that healthy implantation is likely to be in progress). Supplementation with heparinoid (see below) is indicated when there is evidence of concomitant APA’s

.

ASS kann sogar die Chancen einer SS verringern. 😮

<< ASS verduennt das Blut und Blutungen koennen negativ auf eine mgl SS auswirken. Weil Blutungen oder gar Haematome in der GM nicht grad gut sind fuer einen Embryo!

Ausserdem sind Blutungen waehrend der PU auch nicht gut.

Against this background I have now all but abandoned the use of IVIg for immunologic implantation dysfunction associated with NK/CTL activation, supplanting it with IL. On very rare occasions, where IL alone does not achieve the desired result I might recommend combining IVIg with IL therapy.

.

Hm, beides nehmen oder doch IVIGs und bei einer Kryo dann evt IL? *fragend schau*

.

TH-1 Blockers (Enbrel, Humira): I was one of the first to suggest using the TH-1 cytokine blocker, Enbrel (and Humira) forNK cell activation, only to find it to be relatively ineffective in the IVF setting. To date, as far as I am aware, there have not been any convincing reports showing TH-1 blockers to be of real benefit in patients undergoing IVF.

.

Also nix mit Enbrel oder Humira, weils bei IVF nichts bringt. Gut zu wissen!! Der Embryo braucht wohl Th1 um sich einzunisten und wenn man es unterdrueckt ist es nicht gut.

.

Aktive Immu ist meist notwendig bei HLA Sharing, damit der muetterliche Koerper das Embryo als ‚eigen‘ ansieht und damit als schuetzenswert erachtet. Ausserdem reguliert es die NKs runter, und dabei veraendert sich auch das Verhaeltnis Th1/Th2.
Aber IL/IVIG+Cortison reichen auch, um die NKs und den TH Shift zu realisieren.

..

http://haveababy.com/fertility-information/ivf-authority/embryo-quality-embryo-competence-part-iii-testing-the-seed/

Who should have their embryos CGH tested?
As stated above, older women and those with DOR are at increased risk of producing incompetent, aneuploid embryos. However, CGH testing, while improving the efficiency of IVF, does not improve embryo quality. Thus it should never be mandated in all such cases. There is, however, one notable exception, and this applies in cases where “Embryo Banking” is done in order to try and stockpile competent embryos for future dispensation. Here, by selectively stockpiling CGH-normal embryos it is possible to increase the reproductive options available to women who otherwise would clearly be running out of time on the “biological clock”.

..

http://haveababy.com/fertility-information/ivf-authority/ivig-intralipid-therapy-in-ivf/

Currently, probably less than a half dozen Reproductive Immunology Laboratories in the U.S.A are capable of performing the K-562 Target cell test reliably. Both immunoglobulin-G (IVIG) and Intralipid (IL) can successfully down-regulate NKa in the clinical setting.

.

Hier wird auch beschrieben, wie IL/IVIGs wirken: Sie reduzieren NICHT die NKs direkt sondern setzen an der Vorform (parent NKs) an, welche sich dann nicht mehr in die NKs entwickeln koennen, welche schaedlich fuer den EMbryo sind.

Deshalb ist es wichtig VOR einer Progesteronbildung anzusetzen – sprich 7-14 Tage VOR dem TF bzw PU. Da Progerston die Bildung der functional NKs in der GM anregt bzw aktiviert.

..

http://haveababy.com/infertility-information/alloimmune-implantation-dysfunction/

HLA Sharing (DQ)

..

http://haveababy.com/fertility-information/ivf-authority/is-being-overweight-detrimental-to-ivf/

Finally, it is important to emphasize that overweight women are at far greater risk during pregnancy than are women of normal body weight. As previously mentioned, the miscarriage rate is much higher. So is the incidence of diabetes, high blood pressure, preeclampsia, premature labor, surgically assisted deliveries, stillbirth and neonatal death. Maternal complications that occur after birth of the baby (i.e., infection, uterine post partum hemorrhage, etc.) are also much more common. Babies born to such mothers are also at great risk of developing respiratory distress syndrome (RDS). This condition, which ordinarily only occurs in preterm babies, can also occur in the absence of prematurity in such cases. RDS is the most common reason for the newborn having to be admitted to a neonatal intensive care unit, and also the most common cause of death in the first week of life.

..