Patients who conceived without any assistance yet had recurrent pregnancy loss were first studied by Dr. Alan Beer. In these patients, autoantibodies such as phospholipid or thyroid antibodies and specialized lymphocytes like natural killer cells damage the delicate vessels and blood supply of the early placenta, causing clotting in the vessels and pregnancy loss.

For some patients, a reaction of the immunological system may impair the embryo’s ability to attach to the uterine lining and flourish, causing recurrent failed IVF cycles or pregnancy loss. In those with immunological issues, the implanting embryo can elicit an aggressive response, resulting in failure to implant, very early miscarriage (first trimester) or decreased fetal growth in the second and third trimester.

Certain patients who have recurrent loss or repeated failure with IVF treatment may have abnormalities within this system of autoantibodies, natural killer cells, or an inherited thrombophilia that can be identified and treated prior to initiating another IVF cycle. Appropriate testing may suggest therapy as simple as baby aspirin along with Lovenox or an infusion of a nutritional supplement called Intralipid (IL) or a new class of anti-inflammatory medications which antagonize tumor necrosis factor (TNF) these medications include Enbrel, Humira and Simponi.

When trying to identify the root cause of recurrent pregnancy loss, immunological tests help ZFC to identify if the issue lies with the embryo or the uterine environment.

Problems with the Embryo

The most common problem related to the embryo itself is an abnormality of chromosomal number or aneuploidy. Based on the age of the egg, the proportion of embryos that are chromosomally normal ranges from approximately 60% for eggs under age 30 to as low as 5% for eggs at approximately age 45.

Problems with the Uterine Environment

These problems are structural, hormonal or immunological in nature:

  • Structural problems within the uterus may inhibit implantation and include endometrial polyps, submucous fibroids or intracavity adhesions.
  • Both estrogen and progesterone hormones are required for optimum preparation of the uterine lining. During IVF, these hormones are very carefully controlled and supplied, so as to avoid recurrent pregnancy loss in IVF being attributed to hormonal issues.
  • Throughout pregnancy, the embryo, which is genetically different than the uterus itself, is in continuous communication and interaction with the maternal system by way of cytokine proteins secreted by the cells in the uterine lining. When immunological problems occur, these cells don’t send out the proper signals to the embryo, which can cause problems with adhesion and implantation.

When the natural killer cells and cytokines are elevated, our first line of treatment would include paying careful attention to Optimum Health and if the levels remain elevated, additional therapy in the form of Intralipid, the doxycycline protocol or the anit-TNF medications may be indicated.

In addition to applying optimum health measures, the following two protocols can be added to treatment to help with immunological issues and the pregnancy loss associated with it:

Intralipid and IVF

Intralipid is a 20% intravenous fat emulsion, which is usually used as a source of fat and calories for patients requiring parenteral nutrition. Administered intravenously, studies show that Intralipid may enhance implantation and maintenance of pregnancy. In vitro investigations have revealed the ability of Intralipid to suppress the natural killer (NK) cytotoxicity. In a study, Intralipid was shown to be effective in suppressing in vivo abnormal NK cell function, suggesting that Intralipid can be used successfully as a therapeutic option to modulate abnormal NK activity in women with reproductive failure.

Since Intralipid has been used for over 30 years with very few side effects and immense cost savings, Zouves Fertility Center recommends Intralipid as an alternative to intravenous gamma globulin (IVIG.)

Doxycycline Protocol

Studies have shown that certain antibiotics will down-regulate the negative effects of natural killer cells, cytokines gamma interferon and TNF alpha to support nurturing and implantation of the embryo. Other antibiotics, however, can cause an increase in the natural killer cells and cytokines thereby moving patients more to the TH1 side, making the uterine environment more hostile.

The antibiotics that appear to promote implantation by moving to the TH2 state are:

  • Ampicillin
  • Cefoxitin/Gentamycin
  • Doxycycline
  • Zithromax

We believe in the value of immunological testing to find the root cause of recurrent pregnancy loss and then customizing a treatment plan for the greatest possible outcome.

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