The mechanism explaining the association between first-trimester spontaneous miscarriages and the presence of thyroid autoimmunity remains unclear. Glycoprotein hormone receptors form a receptor subfamily, in which significant structural similarity is observed. Cross-reactivity between chorionic gonadotropin (hCG), thyroid-stimulating hormone (TSH) and their receptors (R) is suggested by the thyrotropic action of hCG during pregnancy and in patients with choriocarcinomas as well as by reports of precocious puberty in patients with juvenile hypothyroidism. If TSH can activate LH/CG-R, then, the TSH-R blocking autoantibodies could bind and block LH/CG-R in the corpus luteum through a similar cross-reactivity process. This inhibition could lead to a decrease in steroid hormones production, essential for the support of pregnancy during the first trimester and result in spontaneous miscarriages. This hypothesis, if confirmed, might have major clinical implications, such as the detection of high-risk pregnancies and the elucidation of progesterone role in the prevention of miscarriages.