The answer is no! It is not between the sperm and the egg. IL therapy should be administered in combination with corticosteroids at an adequate dosage, 7—14 days prior to planned embryo transfer, and with alloimmune implantation dysfunction it should ideally be maintained, at least through the 1st half of pregnancy.
Treatment of autoimmune implantation dysfunction requires that IL with corticosteroids be administered only twice, once 7—14 days prior to embryo transfer and then one more time when the beta hCG blood level has shown evidence of an appropriate rise, thereby suggesting that healthy implantation could be in progress. Supplementation with heparinoid is indicated when there is evidence of concomitant antiphospholipid antibodies or certain types of hereditary clotting defects thrombophilias such as a homozygous MTHFR mutation.
Now add to this equation the fact that with a partial DQ alpha match it is probably best to transfer only one embryo at a time in order to reduce the risk that the inadvertent delivery of a DQ alpha matching embryo could potentially cause activation of local uterine NK cell activation that might prejudice the implantation of all embryos being transferred.
Bear in mind that less than embryos are chromosomally normal even in young women, and this decreases further with advancing age. It is advisable to only transfer one embryo at a time in such cases. Indeed, a strong case could be made for full embryo karyotyping using PGS to allow for the selective transfer one at a time of only those embryos that are chromosomally normal euploid. In most cases, this will require biopsying the fresh embryos for PGS testing, allowing them to progress to blastocysts and then cryopreserving these for subsequent single embryo transfer.
This would allow for more competent blastocysts to be available and for a much higher success rate per blastocyst transferred and accordingly, improved IVF outcomes. A gestational surrogate is used when there is a complete DQ alpha match with NK cell activation between the patient and the sperm provider. It has no real merit when there is only a partial match. Ordinarily, provided that an embryo recipient is NK negative, a DQa match between recipient and sperm provider should theoretically not preclude an ensuing pregnancy.
Intralipid IL is a solution of small lipid droplets suspended in water. When administered intravenously, IL provides essential fatty acids, linoleic acid LA , an omega-6 fatty acid, alpha-linolenic acid ALA , an omega-3 fatty acid.
This effect of IL might be due to its ability to suppress pro-inflammatory cellular Type-1 cytokines such as interferon gamma and TNF-alpha,. In this regard it is just as effective as IVIg but at a fraction of the cost and with a far lower incidence of side-effects. Its effect lasts for weeks when administered in early pregnancy. Can in vitro tests done in the laboratory assess for an immediate benefit of Intralipid on NKa?
Since the down-regulation of NKa through IL or IVIg therapy can take several weeks to become detectable, it follows that there is really no benefit in trying to assess the potential efficacy of such treatment by retesting NKa in the laboratory after adding IL or IVIg to the sample.
Partial DQ alpha Match: IVF patients who have NKa associated with a partial alloimmune implantation dysfunction DQ alpha match between partners we use the same IL, infusion as with autoimmune-NKa, only here we prescribe oral prednisone rather than dexamethasone until the 10th week of pregnancy and IL infusions are repeated every weeks following the chemical diagnosis of pregnancy until the 24th week.
Additionally, as alluded to elsewhere in such cases we transfer only a single embryo at a time. Since we presently have no way of determining which embryo carries the matching paternal DQ alpha gene and thus would transfer only one embryo at a time, it follows that the anticipated viable pregnancy rate per cycle will be much lower than with autoimmune implantation dysfunction. Total Complete DQ alpha Match: In cases where the partners have a total alloimmune DQ alpha match with accompanying NKa the chance of a viable pregnancy occurring or if it does resulting in a live birth at term, is so small as to be an indication for using a non-matching sperm donor or resorting to gestational surrogacy would in our opinion be preferable by far.
Contraindications and Cautions with Intralipid Infusion: IL is only contraindicated in conditions associated with severely disordered fat metabolism e. Rarely, hypersensitivity has been observed in patients allergic to soybean protein, egg yolk and egg whites and where fat metabolism may be disturbed e. Adverse Reactions during Infusions of IL Rare : These include transient fever, chills, nausea, vomiting, headache, and back or chest pain with shortness of breath and cyanosis.
It should not be frozen. But those of us who felt morally obligated to many desperate patients who would not conceive without receiving IVIG were facing an uphill battle. The bad press caused by fear mongering took its toll and spawned a malicious controversy. It was only through the introduction of IL less than a decade ago , that the tide began to turn in favor of those patients who required low cost, safe and effective immunotherapy to resolve their IID.
Corticosteroid therapy has become a mainstay in the treatment of most women undergoing IVF. It is believed by most to enhance implantation due to an overall immunomodulatory effect. Some IVF programs prescribe daily oral methyl prednisolone Medrol while others prefer prednisone or dexamethasone, commencing days prior to egg retrieval and continuing until pregnancy is discounted or until the 10th week of pregnancy.
There is compelling evidence that the subcutaneous administration of heparin twice daily or low molecular heparin Clexane, Lovenox once daily, starting with the onset of ovarian stimulation can improve IVF birthrate in women who test positive for APAs and can prevent later pregnancy loss when certain thrombophilias e.
In our opinion, aspirin has little if any value when it comes to IID, and besides, could even reduce the chance of success. The reason for this is that aspirin thins the blood and increases the potential to bleed. There has to date been no convincing data to support their use.
The reason is that the very initial phase of implantation requires a cellular response involving TH-1 cytokines. To block them completely rather than simply restore a TH TH-2 balance as occurs with IL therapy so very early on could compromise rather than benefit implantation. Thus there could be a therapeutic benefit from such therapy.
However, the same benefit can be achieved through the use of IL plus corticosteroids. I have recently had a third failed round using Donor Eggs. I have had my nk cells tested which came back normal. Not further immune testing has been done however, my clinic has me on Tacrolimus, Granocyte, prednisone and intrapilids yet still no pregnancy.
Do you encourage these sorts of medications especially when no elevated Nk cells? And also what testing would you suggest I do now moving forward. The concentration of blood NK cells is irrelevant. Unless tests for immunologic implantation dysfunction IID are performed correctly and conducted by a one of the few reliable reproductive immunology reference laboratory in the United States, treatment will likely be unsuccessful.
In this regard it is most important that the right tests be ordered and that these be performed by a competent laboratory. There are in my opinion only a handful of reliable Reproductive Immunology Laboratories in the world and most are in the U. Also, it is my opinion that far too often, testing is inappropriate with the many redundant and incorrect tests being requested from and conducted by suboptimal laboratories.
Finally for treatment to have the best chance of being successful, it is vital that the underlying type of IID autoimmune IID versus alloimmune be identified correctly and that the type, dosage, concentration and timing of treatments be carefully devised and implemented.
Whenever a patient fails to achieve a viable pregnancy following embryo transfer ET , the first question asked is why! TCR Signaling. G-protein signaling N-RAS regulation pathway. Immune response IL signaling pathway. Immune response NFAT in immune response. Immune response T cell receptor signaling pathway. Allograft Rejection. Browse compounds at ApexBio.
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