R Vissenberg1, M M van Dijk2, E Fliers3, J A M van der Post4, M van Wely2, K W M Bloemenkamp5, A Hoek6, W K Kuchenbecker7, H R Verhoeve8, H C J Scheepers9, S Rombout-de Weerd10, C Koks11, J J Zwart12, F Broekmans13, W Verpoest14, O B Christiansen15, M Post16, D N M Papatsonis17, M F G Verberg18, J Sikkema19, B W Mol20, P H Bisschop3, M Goddijn2. 1. Academic Medical Centre, Centre for Reproductive Medicine, Department of Obstetrics and Gynecology, Amsterdam, The Netherlands. Electronic address: r.vissenberg@amc.uva.nl. 2. Academic Medical Centre, Centre for Reproductive Medicine, Department of Obstetrics and Gynecology, Amsterdam, The Netherlands. 3. Academic Medical Centre, Department of Endocrinology and Metabolism, Amsterdam, The Netherlands. 4. Academic Medical Centre, Department of Obstetrics and Gynecology, Amsterdam, The Netherlands. 5. University Medical Centre Leiden, Department of Obstetrics and Gynecology, Leiden, The Netherlands. 6. University Medical Centre Groningen, University of Groningen, Department of Reproductive Medicine, Groningen, The Netherlands. 7. Isala Clinics, Department of Obstetrics and Gynecology, Zwolle, The Netherlands. 8. Onze Lieve Vrouwe Hospital, Department of Reproductive Medicine, Amsterdam, The Netherlands. 9. University Medical Centre Maastricht, Maastricht University, Department of Reproductive Medicine, Maastricht, The Netherlands. 10. Albert Schweitzer Hospital, Department of Obstetrics and Gynecology, Dordrecht, The Netherlands. 11. Maxima Medical Centre, Department of Obstetrics and Gynecology, Veldhoven, The Netherlands. 12. Deventer Hospital, Department of Obstetrics and Gynecology, Deventer, The Netherlands. 13. University Medical Centre Utrecht, Department of Obstetrics and Gynecology, Utrecht, The Netherlands. 14. University Hospital Brussels, Department of Reproductive Medicine, Brussels, Belgium. 15. Copenhagen University Hospital, Fertility Clinic, Copenhagen, Denmark. 16. Medical Centre Leeuwarden, Department of Obstetrics and Gynecology, Leeuwarden, The Netherlands. 17. Amphia Hospital, Department of Obstetrics and Gynecology, Breda, The Netherlands. 18. Medical Spectrum Twente, Department of Obstetrics and Gynecology, Enschede, The Netherlands. 19. Ziekenhuisgroep Twente, Department of Obstetrics and Gynecology, Hengelo, The Netherlands. 20. The Robinson Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Australia.
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. AIM: 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/ DESIGN: 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.
RCT Entities:
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. AIM: 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/ DESIGN: 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: Tahereh Behroozi-Lak; Ameneh Akbary; Shabnam Vazifekhah; Mohammad Naghavi-Behzad; Mohammad Mirza-Aghazadeh-Attari Journal: J Family Reprod Health Date: 2017-12