Hashimoto's Thyroiditis Negatively Influences Intracytoplasmic Sperm Injection Outcome in Euthyroid Women on T4 Substitution Therapy: A Retrospective Study.

Abstract

Objective: The objective of this study was to analyze the impact of thyroid autoimmunity (TAI) on reproductive outcome parameters of intracytoplasmic sperm injection (ICSI) cycles as compared to TAI-negative ICSI cycles.

Design: In this single in vitro fertilization (IVF) center retrospective study, 86 infertile women with elevated thyroid peroxidase or TGAb levels, but euthyroid after thyroxine replacement (study group), were compared to 69 female patients with no thyroid abnormalities (controls). Following ICSI treatment fertilization rate (FR), clinical pregnancy rate (CPR), miscarriage rate (MR), and live birth rate (LBR) were analyzed.

Materials, setting, methods: All subjects with various infertility factors were treated with ICSI in university-based IVF center. Patients in the study group received thyroxine replacement and were euthyroid at IVF treatment. Before the IVF cycles, endocrinological parameters were uniformly assessed: thyroid function and antibodies, reproductive hormones (anti-Müllerian hormone [AMH], follicular stimulating hormone [FSH], luteinizing hormone, E2, PRL, testosterone, DHEAS, 17-OHP, AD) and OGTT (0-60-120 min glucose and insulin). Following descriptive comparison of laboratory parameters, age-adjusted analyses of FR, CPR, MR, and LBR were performed.

Results: TAI-positive women were older (mean age 35.31 ± 4.95 vs. 32.15 ± 4.87 years; p = 0.002), had higher FSH (8.4 ± 3.4 vs. 7.4 ± 2.32 U/L; p = 0.024), higher E2 (53.94 ± 47.61 vs. 42.93 ± 18.92 pg/mL; p = 0.025) levels, while AMH (2.88 ± 2.62 vs. 3.61 ± 1.69 ng/mL; p = 0.0002) was lower. There were no differences in TSH levels (1.64 ± 0.96 vs. 1.66 ± 0.65 µIU/mL; p = 0.652) between the two groups. FT3 (2.63 ± 0.58 vs. 2.98 ± 0.55 pg/mL; p = 0.002) was lower and FT4 (1.3 ± 0.29 vs. 1.13 ± 0.21 ng/dL; p = 0.0002) was higher in the TAI-positive group, reflecting clinically irrelevant differences. Egg cell counts (6 ± 3.8 vs. 7.5 ± 3.95; p = 0.015) were lower in TAI and remained so following age adjustment. Although the overall ICSI FR did not differ (62.9% vs. 69.1%, p = 0.12), it was lower for patients under 35 with TAI showing decreasing differences in line with age. The CPR (36.04% vs. 69.56%; p < 0.001) and LBR (23.25% vs. 60.86%; p < 0.001) were lower, the MR (35.48% vs. 12.5%; p = 0.024) was higher in the TAI group, and these differences remained after age adjustment.

Limitations: Since the higher age of the study group may interfere with the effect of TAI, age adjustment calculations were necessary to perform to eliminate this confounding factor.

Conclusion: Despite optimal thyroid supplementation in clinical or subclinical hypothyroidism, the presence of TAI negatively influences CPR and is connected to a higher MR, thus resulting in a lower LBR after ICSI. Decreased FR with ICSI in TAI patients may also contribute to poorer outcomes, especially in younger women.