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Immunologic Implantation Dysfunction: A Rational Basis for Treatment


by Geoffrey Sher, M.D.

Currently, with few exceptions, practitioners of Assisted Reproduction tend to attribute “unexplained and/or repeated” IVF failure(s), almost exclusively to poor embryo quality, advocating adjusted protocols for ovarian stimulation and/or gamete and embryo preparation as a potential remedy. The idea that having failed IVF, all that it takes to ultimately succeed is to keep trying over and over using the same recipe is over simplistic. There are numerous non-embryologic that can be responsible for failed IVF. This presentation addresses immunologic factors that cause implantation failure:

The implantation process begins six or seven days after fertilization of the egg. At this time, specialized embryonic cells (i.e., trophoblast), which later becomes the placenta, begin growing into the uterine lining. When the trophoblast and the uterine lining meet, they, along with Immune cells in the lining, become involved in a "cross talk" through mutual exchange of hormone-like substances called cytokines. Because of this complex immunologic interplay, the uterus is able to foster the embryo’s successful growth. Thus, from the earliest stage, the trophoblast establishes the very foundation for the nutritional, hormonal and respiratory interchange between mother and baby. In this manner, the interactive process of implantation is not only central to survival in early pregnancy but also to the quality of life after birth.

Considering its importance, it is not surprising that failure of proper function of this immunologic interaction during implantation has been implicated as a cause of recurrent miscarriage, late pregnancy fetal loss, IVF failure, and infertility. A partial list of immunologic factors that may be involved in these situations includes anti-phospholipid antibodies (APA), antithyroid antibodies (ATA), and, perhaps most importantly, activated natural killer cells (NKa). Presently, these immunologic markers can be adequately measured by only a few (less than a half dozen) highly specialized reproductive immunology laboratories in the United States, from patient blood samples.

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