Levothyroxine treatment and pregnancy outcome in women with subclinical hypothyroidism undergoing assisted reproduction technologies: Systematic review and meta-analysis of RCTs

Abstract

Background: Previous meta-analyses of observational data indicate that pregnant women with subclinical hypothyroidism have an increased risk of adverse pregnancy outcome. Potential benefits of levothyroxine (LT4) supplementation remain unclear, and no systematic review or meta-analysis of trial findings is available in a setting of assisted reproduction technologies (ART). Methods: Relevant trials published until August 2012 were identified by searching MEDLINE, EMBASE, Web of Knowledge, the Cochrane Controlled Trials Register databases and bibliographies of retrieved publications without language restrictions. Results: From 630 articles retrieved, we included three trials with data on 220 patients. One of these three trials stated 'live delivery' as outcome. LT4 treatment resulted in a significantly higher delivery rate, with a pooled relative risk (RR) of 2.76 (95% confidence limits 1.20-6.44; P = 0.018; I2 = 70%), a pooled absolute risk difference (ARD) of 36.3% (3.5-69.0%: P = 0.030) and a summary number needed to treat (NNT) of 3 (1-28) in favour of LT4 supplementation. LT4 treatment significantly lowered miscarriage rate with a pooled RR of 0.45 (0.24-0.82; P = 0.010; I2 = 26%), a pooled ARD of 231.3% (248.2 to 214.5%: P < 0.001) and a summary NNT of 3 (2-7) in favour of LT4 supplementation. LT4 treatment had no effect on clinical pregnancy (RR 1.75; 0.90-3.38; P = 0.098; I2 = 82%). In an ART setting, no data are available on the effects of LT4 supplementation on premature delivery, arterial hypertension, placental abruption or pre-eclampsia. Conclusions: Our meta-analyses provide evidence that LT4 supplementation should be recommended to improve clinical pregnancy outcome in women with subclinical hypothyroidism and/or thyroid autoimmunity undergoing ART. Further research is needed to determine pregnancy outcome after close monitoring of thyroid function to maintain thyroid-stimulating hormone and free T4 levels within the trimester-specific reference ranges for pregnancy. © The Author 2013. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.