Endocrine Abstracts

Background: Thyroid autoimmunity (TAI) is the most important cause of hypothyroidism in the general population, and its prevalence is higher in women of subfertile couples.¹ Women pregnant after an assisted reproductive technology (ART) with TAI carry a higher risk of a first trimester miscarriage rate compared to women without TAI. Several reasons could be underlying such as thyroid dysfunction, older age, an immune imbalance, and the presence of thyrotropin receptor antibodies (TSHR-Ab) that might impede the development of the corpus luteum (the ovarian hypothesis).^1,2 TSHR-Ab can be stimulating (TSAb) or blocking (TBAb) and be present in women with TAI and/or be induced by the ovarian stimulation procedure (OS).³

Aim: In this prospective pilot study, we determined the presence of functional TSHR-Ab before and after OS in ten women with TAI and different causes of subfertility and in one woman without TAI.

Methods: TSH-R-Ab were measured with two established TSAb and TBAb cell-based reporter bioassays with luciferase release as readout according to manufacturer’s instructions (Thyretain®, Quidel, USA). The cAMP-response element (CRE)-dependent luciferase expression levels was quantified in a luminometer.³ In addition, the two new TSAb and TBAb bioassays (Turbo^TM, Quidel) utilize a novel cAMP biosensor that is an engineered form of firefly luciferase. Using this biosensor, luciferase activity is proportional to intracellular cAMP levels. Analyses were performed before, during and at the end of the OS.

Results: Mean (SD) age of the women was 38.8 (± 3.2) years, median (IQR range) BMI 22 (20-28) kg/m², OS cumulative OS dose 1413 (613-2925) IU/l. Median TSH, FT4 and TPO-Ab serum levels were 2.33 (2.23-2.61) mIU/l, 16.8 (14.4-18.5) pmol/l and 152 (86-326) kIU/l, respectively. Fifty percent of women were treated with levothyroxine. During OS, oestradiol levels increased from 40 (26-56) ng/l to 963 (383-5095) ng/l; P < 0.01. Using four different bioassays, no functional TSHR-Ab were detected before or after OS, independent of the method used.

Conclusions: In women with TAI, TSHR-Ab were not detected prior or after OS. The results do not favour the ovarian hypothesis as a cause of increased miscarriage in subfertile women with TAI.

References: 1) Poppe K, Bisschop P, Fugazzola L, Minziori G, Unuane D, Weghofer A. 2021 European Thyroid Association Guideline on Thyroid Disorders prior to and during Assisted Reproduction [published correction appears in Eur Thyroid J. 2021 Jun;10(3):268]. Eur Thyroid J. 2021;9(6):281-295.2) Toulis KA, Goulis DG, Venetis CA, Kolibianakis EM, Tarlatzis BC, Papadimas I. Thyroid autoimmunity and miscarriages: the corpus luteum hypothesis. Med Hypotheses. 2009;73(6):1060-1062.3) Kahaly GJ, Diana T, Olivo PD. TSH RECEPTOR ANTIBODIES: RELEVANCE & UTILITY. Endocr Pract. 2020;26(1):97-106.