Thyroid Autoimmunity & IVF Failure: Linked to Immunologic Implantation Dysfunction?
Between 2% and 5% of women of childbearing age have reduced thyroid hormone activity (hypothyroidism). Women with hypothyroidism often manifest with reproductive failure i.e. infertility, unexplained (often repeated) IVF failure, or recurrent pregnancy loss. The condition is 5-10 times more common in women than in men.
In most cases, hypothyroidism is caused by damage to the thyroid gland resulting from thyroid autoimmunity (TAI) caused by damage done to the thyroid gland by antithyroglobulin and/or antimicrosomal auto-antibodies. The increased prevalence of hypothyroidism and TAI in women is likely the result of a combination of genetic factors, estrogen-related effects and chromosome X abnormalities.
While being the main cause of hypothyroidism, TAI can be present without any coexisting clinical or hormonal evidence of hypothyroidism. Regardless of whether there is such evidence of hypothyroidism or whether the hormone deficiency has been corrected through thyroid hormone supplementation, women with TAI commonly present with reproductive failure. We have reported on the fact (1998, American Journal of Reproductive Immunology) that approximately 50% of women with TAI (regardless of the absence or presence of clinical hypothyroidism) have increased activated Natural Killer cell activity (NKa+) in their blood and that they are the ones that most commonly have reproductive failure.
Since 50% of women with TAI do not have reproductive failure, it is probably not the presence of antithyroid antibodies themselves that causes reproductive failure. Rather, it is more likely a coexisting presence of NKa+ that causes the problem by damaging the early “root system” of the implanting embryo.
In some cases of TAI-induced reproductive failure, pregnancy is lost prior to it being diagnosed through blood or urine beta hCG testing (chemical pregnancies) or before ultrasound confirmation (clinical pregnancies). In other cases, the pregnancy may be lost a little later as a clinical miscarriage. We were among the first to demonstrate and report on the association between NKa+ and reproductive failure in women with TAI. We also showed that in such cases, aside from the need (in those with hypothyroidism) to adequately supplement with thyroid hormone replacement, the administration of intravenous gamma globulin (IVIG) or intralipid (IL) therapy in combination with steroids such as dexamethasone or prednisone (starting at least 4-7 days prior to ovulation or egg retrieval) markedly improves IVF birth rates.
Women with TAI who do NOT have NKa+ do not manifest with reproductive failure and as such do not require or benefit from IVIG or IL +steroid therapy.