Abstract
BackgroundEvidence suggests that subclinical hypothyroidism (SCH) and thyroid autoimmunity (TAI) are associated with adverse pregnancy outcomes. This systematic review and meta-analysis was conducted to determine whether levothyroxine (LT4) supplementation would improve pregnancy outcomes among infertile women with SCH and/or TAI who underwent in vitro fertilization (IVF) or intracytoplastic sperm injection (ICSI).MethodsWe searched databases of PubMed, EMBASE, Web of Science, Cochrane Controlled Trials Register databases, and Clinicaltrials.gov up to April 2018 to identify eligible studies. Studies that focused on the treatment effect of LT4 on pregnancy outcomes of women with SCH and/or TAI who underwent IVF/ICSI were included in the data synthesis. We only included randomized controlled trials (RCTs). Relative risks (RR) and 95% confidence intervals (CI) were calculated using a random-effects model to assess the results of pregnancy outcomes, including clinical pregnancy rate, miscarriage rate, live birth rate and preterm birth rate.ResultsFour published RCTs including 787 infertile couples undergoing IVF/ICSI were included in this meta-analysis. Notably, the study observed no significant associations of LT4 treatment with the clinical pregnancy rate (RR = 1.46, 95% CI: 0.86–2.48), live birth rate (RR = 2.05, 95% CI: 0.96–4.36), or preterm birth rate (RR = 1.13, 95% CI: 0.65–1.96). However, patients receiving LT4 supplementation had a significantly decreased miscarriage rate relative to those receiving a placebo or no treatment (RR = 0.51, 95% CI: 0.32–0.82). A further sub-group analysis showed that LT4 supplementation did not improve the miscarriage rates among patients with SCH (RR = 0.67, 95% CI: 0.39–1.15) or TAI (RR = 0.28, 95% CI: 0.07–1.06).ConclusionsGiven its potential to reduce the miscarriage rate, LT4 supplementation is recommended for infertile women with SCH and/or TAI who are undergoing IVF/ICSI. However, additional population-based RCTs are needed to confirm this recommendation.
Highlights
Evidence suggests that subclinical hypothyroidism (SCH) and thyroid autoimmunity (TAI) are associated with adverse pregnancy outcomes
Many studies have established the association between SCH and/or TAI and adverse pregnancy outcomes, including preeclampsia, placental abruption, miscarriage, preterm birth and neonatal mortality, in both spontaneous pregnancies and those achieved using assisted reproductive technologies (ART) [2, 4,5,6]
The search was limited to human studies published in English, and the following search terms were applied: (subclinical hypothyroidism OR thyroid autoimmunity OR thyroperoxidase antibody (TPO-Ab) OR thyroglobulin antibody (Tg-Ab)) AND (assisted reproductive technology (ART) OR in vitro fertilization (IVF) OR intracytoplasmic sperm injection (ICSI) OR ovarian stimulation) AND AND
Summary
Evidence suggests that subclinical hypothyroidism (SCH) and thyroid autoimmunity (TAI) are associated with adverse pregnancy outcomes. This systematic review and meta-analysis was conducted to determine whether levothyroxine (LT4) supplementation would improve pregnancy outcomes among infertile women with SCH and/or TAI who underwent in vitro fertilization (IVF) or intracytoplastic sperm injection (ICSI). Subclinical hypothyroidism (SCH) is a common mild thyroid disorder among women of childbearing age, with a prevalence of 3–8% [1, 2]. Thyroid autoimmunity (TAI), defined as the presence of thyroid autoantibodies, antithyroperoxidase antibody (TPO-Ab), or antithyroglobulin antibody (Tg-Ab), is the most common cause of hypothyroidism among women of childbearing age [3]. Levothyroxine (LT4) supplementation may attenuate the risks of adverse pregnancy outcomes
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