L26/P-781 The impact of levothyroxine initiation before frozen embryo transfer on fertility outcomes in infertile women with subclinical hypothyroidism: a retrospective cohort study

Abstract Study question In women with subclinical hypothyroidism (SCH) undergoing frozen embryo transfer (FET), does levothyroxine initiation before FET increase live birth rates (LBR)? Summary answer Levothyroxine initiation before FET was not associated with higher LBR in women with SCH, despite improved embryological outcomes. What is known already SCH is common among women undergoing assisted reproduction (ART), but its management before ART remains controversial. While levothyroxine clearly benefits overt hypothyroidism, evidence for treating SCH is inconsistent, particularly for live births. Prior studies have reported inconsistent associations between SCH and implantation, miscarriage, and live births, partly due to heterogeneous thyroid-stimulating hormone (TSH) cut-offs, differences in thyroid autoimmunity status, and variation in ART protocols. Consequently, whether levothyroxine treatment for SCH improves clinically meaningful outcomes, particularly LBR in women undergoing FET, is still uncertain. Study design, size, duration Retrospective cohort study conducted at a tertiary in vitro fertilisation centre, using routinely collected clinical data from 1 January 2019 to 31 December 2024 (n = 412; levothyroxine: n = 198; control: n = 214). Baseline was defined as the first thyroid function test meeting SCH criteria (TSH 4.2–10.0 mIU/L and normal free thyroxine level), according to the 2021 European Thyroid Association guidelines. Participants/materials, setting, methods Women aged 18–45 with SCH were included, excluding overt hypothyroidism or recent thyroid-affecting medication use. Levothyroxine (25–50 µg/day) was initiated within 2 months before FET and titrated every 2–4 weeks (target TSH <2.5 mIU/L before FET). The primary outcome was LBR after one FET. Main results and the role of chance A total of 412 women were analysed (levothyroxine: n = 198; control: n = 214). Baseline TSH was 5.6±1.3 mIU/L in the levothyroxine group and 5.2±1.1 mIU/L in controls. Prior to FET, mean TSH in treated women was 1.4±0.6 mIU/L, consistent with the treatment target. The LBR was 43.9% (87/198) in the levothyroxine group versus 39.3% (84/214) in the control group (risk difference 4.6%, p = 0.387). Univariate analysis showed no significant difference in LBR between groups (OR 1.21, 95% CI 0.82–1.80; p = 0.337). After adjustment for baseline confounders (age, infertility duration, ovarian reserve markers, and transfer characteristics), levothyroxine initiation was not significantly associated with LBR (aOR 1.59, 95% CI 0.69–3.69; p = 0.278). However, the levothyroxine group showed significantly higher numbers of fertilized oocytes (p = 0.027), total Day-3 embryos (p = 0.015), good-quality Day-3 embryos (p = 0.027), and blastocysts (p = 0.044). No significant differences were observed between groups regarding biochemical pregnancy, clinical pregnancy, early miscarriage, and ongoing pregnancy rates. Limitations, reasons for caution Limitations include the retrospective nature of the study, potential residual confounding, and unrecorded variables such as treatment adherence. Thyroid peroxidase antibody status was not routinely available; therefore subgroup analyses were limited based on thyroid autoimmunity. Wider implications of the findings Routine levothyroxine initiation for SCH prior to FET may not yield clinical benefits in terms of live birth outcomes. Future research should focus on identifying specific subgroups and defining optimal treatment thresholds, particularly women with thyroid autoimmunity and/or higher baseline TSH who may benefit from intervention. Trial registration number No