A relook at the relevance of thyroid stimulating hormone and thyroid autoimmunity for pregnancy outcomes: Analyses of randomized control trials data from Pregnancy in Polycystic Ovary Syndrome and Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation.

Objective: We examined if thyroid autoimmunity is relevant to the relationship between maternal thyroid stimulating hormone (TSH) levels and pregnancy outcomes.
Setting: Not applicable.
Design: Retrospective cohort analysis of data from 2 randomized controlled trials (RCTs).
Patients: Participants of the Pregnancy in Polycystic Ovary Syndrome (PPCOS II, n = 746) and the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS, n = 832 with unexplained infertility) RCTs.
Intervention(s): Pre-RCT intervention levels of TSH at threshold of ≥2.0 mU/L and thyroid peroxidase antibody (TPO-Ab) at titer threshold of ≥30 U/mL.
Main Outcome Measures: Live birth (primary outcome), pregnancy loss, and preterm birth (secondary outcomes). Generalized linear model (GLM) analyses examined the relationship between exposure to TSH and TPO-Ab at specified thresholds with the specified outcomes; covariates adjusted for included age, body mass index, race, ethnicity, education, smoking, duration of infertility, PCOS (vs. unexplained infertility), and randomized intervention arm in the respective RCTs.
Results: On adjusted analyses, live birth was significantly reduced in the exposed population (those with TSH ≥2.0 mU/L and TPO-Ab ≥30 U/mL, n = 117/1,578, 7.4%, adjusted risk ratio [ARR]: 0.55; 95% CI: 0.35-0.87) compared with the unexposed (those with TSH <2.0 mU/L and TPO-Ab <30 U/mL, n = 865/1,578, 54.8%). Furthermore, the risk of pregnancy loss and of early preterm birth (<32 weeks) was significantly higher in the exposed compared with the unexposed (ARR for pregnancy loss was 1.66; 95% CI: 1.14-2.42, and ARR for early preterm birth was 4.82, 95% CI: 1.53-15.19).
Conclusions: In women with TPO-Ab titers ≥30 U/mL, pregnancy outcomes may be compromised at TSH threshold of ≥2 mU/L. These findings of an interaction between TSH and TPO for pregnancy outcomes merit further investigation in prospective studies.
Trial Registration Number: NCT00719186 and NCT01044862.
(Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)