Thyroid axis dysregulation during in vitro fertilization in hypothyroid-treated patients

Background: While there is a large body of evidence showing a significant impact of controlled ovarian hyperstimulation (COH) on thyroid function in euthyroid patients undergoing in vitro fertilization (IVF), information on the effect of this treatment on thyroid axis equilibrium in hypothyroid-treated patients is insufficient. The goal of this prospective study was to investigate serum thyroid-stimulating hormone (TSH) modifications in hypothyroid-treated patients during IVF. Methods: Hypothyroid-treated women selected for IVF between November 2010 and December 2011 were considered for study entry. They were eligible if serum TSH tested the month preceding the IVF cycle was 0.4-2.5 mIU/L. Additional inclusion criteria were as follows: (1) a certified diagnosis of clinical or subclinical hypothyroidism; (2) consumption of at least 25μg of levothyroxine daily; (3) serum free triiodothyronine and free thyroxine tested the month preceding the IVF cycle within the reference range; (4) no previous IVF cycles; (5) regular menstrual cycles; and (6) day 3 serum follicle-stimulating hormone <12IU/mL and anti-Müllerian hormone >0.5ng/mL. Serum TSH was tested at three time points: between day 1 and day 8 of the cycle during the month preceding the start of controlled ovarian hyperstimulation (COH), at the time of human chorionic gonadotropin (hCG) administration and at 16 days after hCG administration. Results: Seventy-two women met our selection criteria. The serum levels of TSH at basal assessment, at the time of hCG administration, and at 16 days after hCG administration were 1.7±0.7, 2.9±1.3, and 3.2±1.7 mIU/L, respectively. All pairwise comparisons were statistically significant. Serum TSH exceeded the threshold of 2.5 mIU/L in 46 subjects at the time of hCG administration (64%, [CI: 53-75%]) and in 49 subjects 16 days after hCG administration (68%, [CI: 57-79%]). Conclusions: Serum TSH increased considerably during COH in adequately treated hypothyroid women undergoing IVF. We suggest strictly monitoring these women during IVF cycles and, if necessary, promptly adjusting the levothyroxine dose. This is the most pragmatic approach but, to date, it is not supported by clinical evidence. Further studies aimed at clarifying the most suitable therapeutic strategy are thus warranted.