A re-look at the relevance of TSH and thyroid autoimmunity for pregnancy outcomes: Analyses of RCT data from PPCOS II and AMIGOS.

Abstract

We examined if thyroid autoimmunity is relevant to the relationship between maternal TSH levels and pregnancy outcomes. Retrospective cohort analysis of data from two randomized controlled trials (RCTs). 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. Pre-trial intervention levels of thyroid stimulating hormone (TSH) at threshold of ≥2.0 mU/L and thyroid peroxidase antibody (TPO-Ab) at titer threshold of ≥30 U/mL. 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 (versus unexplained infertility) and randomized intervention arm in the respective RCTs. 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= 117/1578, 7.4%, adjusted risk ratio [ARR] 0.55, 95% CI 0.35- 0.87) compared to the unexposed (those with TSH <2.0 mU/L and TPO-Ab <30 U/mL, n=865/1578, 54.8%). Furthermore, the risk of pregnancy loss and of early preterm birth (<32 weeks) was significantly higher in the exposed compared to 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). 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.