Thyroid function during controlled ovarian hyperstimulation as part of in vitro fertilization

Abstract

Objective: To determine the exact nature and timing of alterations in thyroid function throughout controlled ovarian hyperstimulation (COH).

Design: Prospective cohort study.

Setting: University fertility clinic.

Patient(s): Fifty-seven women undergoing COH as part of planned in vitro fertilization.

Intervention(s): None.

Main outcome measure(s): Timing and magnitude of change in serum thyroid hormones, including TSH, total and free T(4), E(2), and thyroxine-binding globulin (TBG), measured at six time points from before stimulation to 2 weeks after serum pregnancy test.

Result(s): Geometric mean serum TSH increased during stimulation, peaking 1 week after hCG administration compared with baseline (2.44 vs. 1.42 mIU/L), as did free T(4) (1.52 vs. 1.38 ng/dL) and TBG (32.86 vs. 21.52 μg/mL). Estradiol levels increased, peaking at hCG administration (1743.21 vs. 71.37 pg/mL). Of 50 women with baseline TSH ≤ 2.5 mIU/L, 22 (44.0%) had a subsequent rise in TSH to >2.5 during or after COH. The pattern of change over time in TSH concentrations was significantly influenced by baseline hypothyroidism and whether pregnancy was achieved.

Conclusion(s): COH led to significant elevations in TSH, often above pregnancy appropriate targets. These findings were particularly evident in women with preexisting hypothyroidism and may have important clinical implications for screening and thyroid hormone supplementation.

FIGURE 1

(Top) TSH over time by hypothyroid status. (Bottom) Free T₄ over time by hypothyroid status. Geometric mean values with standard error bars shown. For both: euthyroid–TPOAb negative (n = 45) and hypothyroid-treated (n = 9). *P≤.01 for within-group comparisons at each time point compared with time 1. ^†P≤.01 for between-group comparisons at each time point. Time points: 1) before stimulation; 2) 4–7 days after initiating stimulation; 3) at hCG administration; 4) 1 week after hCG; 5) at pregnancy test; and 6) 2 weeks after pregnancy test.

FIGURE 2

(Top) Estradiol over time by hypothyroid status. (Bottom) TBG over time by hypothyroid status. Geometric mean values with standard error bars shown. For both: euthyroid-TPOAb negative (n = 45) and hypothyroid-treated (n = 9). *P≤.01 for within-group comparisons at each time point compared with time 1. ^†P≤.01 for between-group comparisons at each time point. Time points: 1) before stimulation; 2) 4–7 days after initiating stimulation; 3) at hCG administration; 4) 1 week after hCG; 5) at pregnancy test; and 6) 2 weeks after pregnancy test.

FIGURE 3

(Top) TSH over time by pregnancy (pregnant [n = 19] vs. not pregnant [n = 38]). *P≤.01 for within-group comparisons at each time point compared with time 1. ^†P≤.01 for between-group comparisons at each time period. (Bottom) TSH over time in participants that became pregnant (16 euthyroid–TPOAb-negative participants and two hypothyroid participants). Both hypothyroid participants had an increase in LT₄ dose between times 5 and 6 (#). Geometric mean values with standard error bars shown. Time points: 1) before stimulation; 2) 4–7 days after initiating stimulation; 3) at hCG administration; 4) 1 week after hCG; 5) at pregnancy test; and 6) 2 weeks after pregnancy test.