Impaired Outcome of Controlled Ovarian Hyperstimulation in Women with Thyroid Autoimmune Disease

Background: Controlled ovarian hyperstimulation (COH) is a crucial step of assisted reproductive technology (ART). Thyroid dysfunction and autoimmune thyroid disease (ATD) may negatively affect the outcome of ART, but the underlying mechanisms are still poorly understood. Our aim was to evaluate the respective role of ATD and thyroid function, as assessed by serum thyrotropin (TSH), on the early outcome of COH.

Methods: In total, 262 (202 ATD-negative and 60 ATD-positive) euthyroid subfertile women underwent ART. Before COH, serum follicle-stimulating hormone (FSH), luteinizing hormone, and estradiol (E2) were measured at cycle day 3, and progesterone at cycle day 21. At oocyte pickup and at embryo transfer, we evaluated the performance of recombinant FSH (r-FSH), as assessed by serum E2 concentration/total administered r-FSH units (E2/r-FSH) ratio and by oocyte quality.

Results: At both oocyte pickup and embryo transfer, the performance of r-FSH was significantly poorer in ATD-positive than in ATD-negative women. In the ATD-positive group, women with a TSH <2.5 mIU/L displayed a higher serum E2 concentration at oocyte pickup, a higher E2/r-FSH ratio, and a greater number of mature metaphase II oocytes than women with a TSH >2.5 mIU/L. When ATD-positive women were divided into quartiles according to their serum TSH level, both the ovarian response to r-FSH and the number of mature metaphase II oocytes significantly increased from the lowest to the highest quartiles of serum TSH concentration.

Conclusions: ATD has a negative effect on the early outcome of COH, but this negative influence may be avoided with adequate levothyroxine therapy aimed at keeping TSH <2.5 mU/L. Thyroid antibodies and serum TSH should be checked in any woman undergoing ART.