title: Effect of levothyroxine on live birth rate in euthyroid women with recurrent miscarriage and TPO antibodies (T4-LIFE study).
abstract: BACKGROUND
  Thyroid peroxidase antibodies (TPO-Ab) in euthyroid women are associated with recurrent miscarriage (RM) and other pregnancy complications such as preterm birth. It is unclear if treatment with levothyroxine improves pregnancy outcome.
  
  
  OBJECTIVE
  The aim of this study is to determine the effect of levothyroxine administration on live birth rate in euthyroid TPO-Ab positive women with recurrent miscarriage.
  
  
  METHODS
  We will perform a multicenter, placebo controlled randomized trial in euthyroid women with recurrent miscarriage and TPO-Ab. Recurrent miscarriage is defined as two or more miscarriages before the 20th week of gestation. The primary outcome is live birth, defined as the birth of a living fetus beyond 24weeks of gestation. Secondary outcomes are ongoing pregnancy at 12weeks, miscarriage, preterm birth, (serious) adverse events, time to pregnancy and survival at 28days of neonatal life. The analysis will be performed according to the intention to treat principle. We need to randomize 240 women (120 per group) to demonstrate an improvement in live birth rate from 55% in the placebo group to 75% in the levothyroxine treatment group. This trial is a registered trial (NTR 3364, March 2012). Here we discuss the rationale and design of the T4-LIFE study, an international multicenter randomized, double blind placebo controlled, clinical trial aimed to assess the effectiveness of levothyroxine in women with recurrent miscarriage and TPO-Ab.
authors.affiliation: Academic Medical Centre, Centre for Reproductive Medicine, Department of Obstetrics and Gynecology, Amsterdam, The Netherlands. Electronic address: r.vissenberg@amc.uva.nl.
authors.forename: R
authors.initials: R
authors.lastname: Vissenberg
authors.affiliation: Academic Medical Centre, Centre for Reproductive Medicine, Department of Obstetrics and Gynecology, Amsterdam, The Netherlands.
authors.forename: M M
authors.initials: MM
authors.lastname: van Dijk
authors.affiliation: Academic Medical Centre, Department of Endocrinology and Metabolism, Amsterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Fliers
authors.affiliation: Academic Medical Centre, Department of Obstetrics and Gynecology, Amsterdam, The Netherlands.
authors.forename: J A M
authors.initials: JAM
authors.lastname: van der Post
authors.affiliation: Academic Medical Centre, Centre for Reproductive Medicine, Department of Obstetrics and Gynecology, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Wely
authors.affiliation: University Medical Centre Leiden, Department of Obstetrics and Gynecology, Leiden, The Netherlands.
authors.forename: K W M
authors.initials: KWM
authors.lastname: Bloemenkamp
authors.affiliation: University Medical Centre Groningen, University of Groningen, Department of Reproductive Medicine, Groningen, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Hoek
authors.affiliation: Isala Clinics, Department of Obstetrics and Gynecology, Zwolle, The Netherlands.
authors.forename: W K
authors.initials: WK
authors.lastname: Kuchenbecker
authors.affiliation: Onze Lieve Vrouwe Hospital, Department of Reproductive Medicine, Amsterdam, The Netherlands.
authors.forename: H R
authors.initials: HR
authors.lastname: Verhoeve
authors.affiliation: University Medical Centre Maastricht, Maastricht University, Department of Reproductive Medicine, Maastricht, The Netherlands.
authors.forename: H C J
authors.initials: HCJ
authors.lastname: Scheepers
authors.affiliation: Albert Schweitzer Hospital, Department of Obstetrics and Gynecology, Dordrecht, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Rombout-de Weerd
authors.affiliation: Maxima Medical Centre, Department of Obstetrics and Gynecology, Veldhoven, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Koks
authors.affiliation: Deventer Hospital, Department of Obstetrics and Gynecology, Deventer, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Zwart
authors.affiliation: University Medical Centre Utrecht, Department of Obstetrics and Gynecology, Utrecht, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Broekmans
authors.affiliation: University Hospital Brussels, Department of Reproductive Medicine, Brussels, Belgium.
authors.forename: W
authors.initials: W
authors.lastname: Verpoest
authors.affiliation: Copenhagen University Hospital, Fertility Clinic, Copenhagen, Denmark.
authors.forename: O B
authors.initials: OB
authors.lastname: Christiansen
authors.affiliation: Medical Centre Leeuwarden, Department of Obstetrics and Gynecology, Leeuwarden, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Post
authors.affiliation: Amphia Hospital, Department of Obstetrics and Gynecology, Breda, The Netherlands.
authors.forename: D N M
authors.initials: DNM
authors.lastname: Papatsonis
authors.affiliation: Medical Spectrum Twente, Department of Obstetrics and Gynecology, Enschede, The Netherlands.
authors.forename: M F G
authors.initials: MFG
authors.lastname: Verberg
authors.affiliation: Ziekenhuisgroep Twente, Department of Obstetrics and Gynecology, Hengelo, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Sikkema
authors.affiliation: The Robinson Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Australia.
authors.forename: B W
authors.initials: BW
authors.lastname: Mol
authors.affiliation: Academic Medical Centre, Department of Endocrinology and Metabolism, Amsterdam, The Netherlands.
authors.forename: P H
authors.initials: PH
authors.lastname: Bisschop
authors.affiliation: Academic Medical Centre, Centre for Reproductive Medicine, Department of Obstetrics and Gynecology, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Goddijn
keywords: Levothyroxine; Live birth rate; Preterm birth; Recurrent miscarriage; TPO antibodies; Thyroid autoimmunity