Question posed by by Patient X: Can oral steroids (prednisone) and IL therapy be done without IVF? I have had 2 failed IUI’s 2 years ago, but I do not like taking ovulation stimulating hormones. I have endometriosis (not sure of what stage), am not currently working with an RE, and have been TTC for 6 years. I have a higher than normal for TTC TSH level (3.5-4), am 34Y/O, totally normal and regular periods with ovulation almost every month, and husband checks out with good numbers/motility/morphology. I’ve never been tested for an immunologic implantation dysfunction (IID)  or for increased natural killer (NK) cells  but I’ve only ever been “late” 3 or 4 times in the past 6 years of trying. I have other autoimmune issues such as chronic allergies and reactionary lymph nodes in my neck near my thyroid gland. Your research on all of this has really answered a lot of my thoughts already,  but thank you for your time Dr. __________________________________ My Response:

  • Immunologic Implantation Dysfunction (IID)
  • Autoimmune IID: Autoimmune implantation dysfunction, most commonly presents with presumed “infertility” due to such early pregnancy losses that the woman did not even know she was pregnant in the first place. Sometimes there as an early miscarriage. Tests required are: a) blood levels of all IgA, IgG and IgM-related antiphospholipid antibodies (APA’s) directed against six or seven specific phospholipids, b) both antithyroid antibodies (antithyroid and antimicrosomal antibodies), c) a comprehensive reproductive immunophenotype (RIP) and, c) most importantly, assessment of Natural Killer (NK) cell activity (rather than concentration) by measuring by their killing, using the K-562 target cell test and/or uterine cytokine measurement. As far as the ideal environment for performing such tests, it is important to recognize that currently there are only about 5 or 6,  Reproductive Immunology Reference Laboratories in the U.S capable of reliably analyzing  the required elements with a sufficient degree of  sensitivity and specificity (in my opinion).
  • Alloimmune IID: While alloimmune Implantation usually presents with a history of unexplained (usually repeated) miscarriages or secondary infertility (where the woman conceived initially and thereupon was either unable to conceive started having repeated miscarriages it can also present as “presumed” primary infertility. Alloimmune dysfunction is diagnosed by testing the blood of both the male and female partners for matching DQ alpha genes and NK/CTL activation. It is important to note that any DQ alpha match (partial or complete) will only result in IID when there is concomitant NK/CTL activation (see elsewhere on this blog).

Central to making a diagnosis of IID is the appropriate interpretation of natural killer cell activity (NKa) .In this regard, one of the commonest and most serious errors, is to regard the blood concentration of natural killer cells as being significant. Rather it is the activity (toxicity) of NK cells that matters as mentioned. The tests used to diagnose Nka+ are: a) the K-562 target cell blood test and the detection of increased  TH-1 cytokines (TNF-alpha and Interferon Gamma in endometrial cells (following timed endometrial biopsy).

  • The effect of endometriosis on pregnancy potential.
  1. The toxic peritoneal factor: Endometriotic deposits in the pelvis invariably produce and release toxins” into the pelvic secretions that coat the surface of the membrane (the peritoneum) that envelops all abdominal and pelvic organs, including the uterus, tubes and ovaries. These toxins are referred to as “the peritoneal factor”. Following ovulation, the egg(s) must pass from the ovary (ies), through these toxic secretions to reach the sperm lying in wait in the outer part the fallopian tube (s) tube(s) where, the sperm lie in waiting. In the process of going from the ovary(ies) to the Fallopian tube(s) these eggs become exposed to the “peritoneal toxins” which alter s the envelopment of the egg (i.e. zona pellucida) making it much less receptive to being fertilized by sperm. As a consequence, if they are chromosomally normal such eggs are rendered much less likely to be successfully fertilized. Since almost all women with endometriosis have this problem, it is not difficult to understand why these women are far less likely to conceive following ovulation (whether natural or induced through ovulation induction). This “toxic peritoneal factor impacts on eggs that are ovulated whether spontaneously (as in natural cycles) or following the use of fertility drugs and serves to explain why the chance of pregnancy is so significantly reduced in normally ovulating women with endometriosis.
  2. IID associated with endometriosis: Another consideration is that about one third of women who have endometriosis will also have an immunologic implantation dysfunction (IID) linked to activation of uterine natural killer cells (NKa). This will require selective immunotherapy with Intralipid infusions, and/or heparinoids (e.g. Clexane/Lovenox) that is much more effectively implemented in combination with IVF.

It is also inadvisable to use Intralipid/steroid treatment without IVF treatment, otherwise there would likely be a need receive monthly infusions of IL and uninterrupted steroid therapy over an extended period of time, until pregnancy occurs. In the final analysis, it is my opinion that you should be thoroughly evaluated for an IID and it should be determined whether this is autoimmune or alloimmune in nature and then proceed to IVF.