When a woman is not able to conceive after one or more attempts at IVF with no apparent reason, she may feel heightened anguish. She may then broaden her research efforts with a determined resolve, even exploring unconventional treatments. She may end up considering immunological testing and treatment. It is easy for patients to scapegoat the body's immune system when apparently healthy looking embryos fail to implant, or a pregnancy is thwarted for unknown reasons. Autoimmune factors related to recurrent pregnancy loss (RPL) have been fairly well studied, resulting in treatment methods that are relatively standard. On the other hand, implicating the immune system for repeated IVF failures represents an area of medicine that can be subject to abuse. Practitioners of reproductive endocrinology in the U.S. as well as Great Britain consider this one of the more controversial topics in their field. There is no shortage of data analyzing the role of immunology in reproductive success or failure. A number of comprehensive studies in the mid- to late1990s were undertaken to identify a potential cause and effect relationship between abnormal immune test results associated with reproductive failure. Yet the tests reached the same conclusions; the most rigorous studies failed to provide a correlation. Today many years after most reproductive endocrinologists might have thought the topic was put to rest, women with greater research capabilities on the internet who actively seek answers for their fertility problems continue to come across offers of clinical immunological investigations and treatments that lack true scientific basis. As pointed out by the Royal College of Obstetricians and Gynecologists, *"Praying to Artemis of Ephesus, a goddess associated with fertility, might be as useful as undergoing some of the fertility tests offered on the Internet".*Patients are rarely informed that there is no standardized testing methodology among laboratories, so the interpretation of test results (normal, borderline, or abnormal) is frequently inconsistent. If and when therapies are administered, many are designed to modify the immune system (i.e. glucocorticoid treatment, intravenous immunoglobulin, and peripheral leukocyte immunization) or to compensate for the suspected effects of the immune defect (i.e. heparin or aspirin to reduce thrombophilia from thrombogenic autoantibodies). Given the lack of strong scientific proof of meaningful associations between abnormal immune testing and adverse reproductive outcome, combined with the poor quality of the standards of such tests, PFC physicians maintain a packet of information for our patients who inquire about potential immunological causes to their infertility. In the next issue of Fertility Flash, we will provide a follow-up article that will include more detailed descriptions of the tests that have been conducted as well as an introductory description of what is considered viable immunological tests and treatments for RPL, versus those that are considered more controversial for repeated IVF failure.
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