Influência da autoimunidade tireoidiana nos desfechos reprodutivos femininos desde a fertilização até o pré-natal: uma revisão guarda-chuva

Abstract

Introduction: Thyroid autoimmunity (TIA) has been associated with adverse reproductive outcomes, such as infertility, spontaneous abortion, preterm birth, and gestational complications. Despite its high prevalence in women of reproductive age, the pathophysiological mechanisms and clinical impact of this possible relationship remain uncertain due to the methodological heterogeneity of existing studies. Objective: To synthesize the evidence available in systematic reviews on the influence of TIA on female reproduction, from fertilization to the prenatal period, and to evaluate the efficacy of therapeutic interventions. Methods: An umbrella review was carried out, reported following the PRISMA 2020 guidelines, with a protocol prospectively registered in PROSPERO (CRD42024624099). The searches covered the PubMed, Cochrane, and Embase databases (up to August/2024). Systematic reviews that evaluated stages such as ovarian reserve, fertility, spontaneous abortion, maternal-fetal complications, and efficacy of levothyroxine and assisted reproductive therapies (ART) were selected. The degree of confidence in the methodological quality was assessed by the AMSTAR 2 tool. Results: Thirty-four systematic reviews were included. The synthesis of their results revealed that women with TIA have a significant reduction in ovarian reserve markers and an increased risk of infertility. In addition, immune dysfunction and the presence of autoantibodies can impair follicular maturation. TPOAb/TgAb positivity also increases the risk of spontaneous abortion and recurrent pregnancy loss. The proposed mechanisms include immune dysregulation, changes in embryo implantation, and trophoblastic dysfunction. Complications such as premature birth and gestational diabetes mellitus (GDM) were also more frequent, especially in women with associated clinical and laboratory thyroid dysfunction. Data on intrauterine growth restriction and fetal thyrotoxicosis are limited and inconclusive. Levothyroxine therapy has clear benefits in women with overt thyroid dysfunction (reduction of miscarriage and preterm birth), but the evidence is inconclusive for euthyroid women. Women with TIA undergoing IVF/ICSI have a higher risk of miscarriage and a lower live birth rate, but universal screening before the procedure is not consensual. Of the total reviews, 70.6% had a low/critically low confidence level in methodological quality, mainly due to the lack of prior registration in a review database and critical assessment of risk of bias. Conclusion: TIA is associated with adverse reproductive outcomes, but establishing a precise causal relationship remains a challenge due to confounding factors, such as age, TSH levels and polyautoimmunity, present in the population samples evaluated by the reviews. The use of levothyroxine is recommended only for women with overt thyroid dysfunction, while its role in euthyroid women remains uncertain. Future systematic reviews need to prioritize more methodologically reliable designs, in the same way that sequential original studies investigate reproductive outcomes not covered by this work, especially those of cardiovascular origin, for the possibility of influence of TIA, with careful attention to the homogeneity of diagnostic laboratory cuts.