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Open Access Study protocol

The OPTIMIST study: optimisation of cost effectiveness through individualised FSH stimulation dosages for IVF treatment. A randomised controlled trial

Theodora C van Tilborg1*, Marinus JC Eijkemans2, Joop SE Laven3, Carolien AM Koks4, Jan Peter de Bruin5, Gabrielle J Scheffer6, Ron JT van Golde7, Kathrin Fleischer8, Annemieke Hoek9, Annemiek W Nap10, Walter KH Kuchenbecker11, Petra A Manger12, Egbert A Brinkhuis13, Arne M van Heusden14, Alexander V Sluijmer15, Arie Verhoeff16, Marcel HA van Hooff17, Jaap Friederich18, Jesper MJ Smeenk19, Janet Kwee20, Harold R Verhoeve21, Cornelis B Lambalk22, Frans M Helmerhorst23, Fulco van der Veen24, Ben Willem J Mol24, Helen L Torrance1 and Frank JM Broekmans1

Author Affiliations

1 Department of Reproductive Medicine and Gynaecology, University Medical Centre Utrecht, University of Utrecht, Utrecht, The Netherlands

2 Julius Centre for Health Sciences and Primary care, University Medical Centre Utrecht, Utrecht, The Netherlands

3 Department of Obstetrics and Gynaecology, Division of Reproductive Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands

4 Department of Obstetrics and Gynaecology, Maxima Medical Centre, Veldhoven, The Netherlands

5 Department of Obstetrics and Gynaecology, Jeroen Bosch Hospital, Den Bosch, The Netherlands

6 Department of Obstetrics and Gynaecology, Gelre Hospital, Apeldoorn, The Netherlands

7 Department of Obstetrics and Gynaecology, Maastricht University Medical Centre, University of Maastricht, Maastricht, The Netherlands

8 Department of Obstetrics and Gynaecology, University Medical Centre St Radboud, Nijmegen, The Netherlands

9 Department of Obstetrics and Gynaecology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands

10 Department of Obstetrics and Gynaecology, Rijnstate Hospital, Arnhem, The Netherlands

11 Department of Obstetrics and Gynaecology, Isala Clinics, Zwolle, The Netherlands

12 Department of Obstetrics and Gynaecology, Diakonessen Hospital Utrecht, Utrecht, The Netherlands

13 Department of Obstetrics and Gynaecology, Meander Medical Centre, Amersfoort, The Netherlands

14 Department of Obstetrics and Gynaecology, St Antonius Hospital, Nieuwegein, The Netherlands

15 Department of Obstetrics and Gynaecology, Wilhelmina Hospital, Assen, The Netherlands

16 Department of Obstetrics and Gynaecology, Maasstad Hospital, Rotterdam, The Netherlands

17 Department of Obstetrics and Gynaecology, St Fransiscus Hospital, Rotterdam, The Netherlands

18 Department of Obstetrics and Gynaecology, Gemini Hospital, Den Helder, The Netherlands

19 Department of Obstetrics and Gynaecology, St Elisabeth Hospital, Tilburg, The Netherlands

20 Department of Obstetrics and Gynaecology, St Lucas Andreas Hospital, Amsterdam, The Netherlands

21 Department of Obstetrics and Gynaecology, Onze Lieve Vrouwe Hospital, Amsterdam, The Netherlands

22 Department of Obstetrics and Gynaecology, VU University Medical Centre, Amsterdam, The Netherlands

23 Department of Obstetrics and Gynaecology, Leids University Medical Centre, University of Leiden, Leiden, The Netherlands

24 Department of Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands

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BMC Women's Health 2012, 12:29  doi:10.1186/1472-6874-12-29

Published: 18 September 2012

Abstract

Background

Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH). FSH is usually administered in a standard dose. However, due to differences in ovarian reserve between women, ovarian response also differs with potential negative consequences on pregnancy rates. A Markov decision-analytic model showed that FSH dose individualisation according to ovarian reserve is likely to be cost-effective in women who are eligible for IVF. However, this has never been confirmed in a large randomised controlled trial (RCT). The aim of the present study is to assess whether an individualised FSH dose regime based on an ovarian reserve test (ORT) is more cost-effective than a standard dose regime.

Methods/Design

Multicentre RCT in subfertile women indicated for a first IVF or intracytoplasmic sperm injection cycle, who are aged < 44 years, have a regular menstrual cycle and no major abnormalities at transvaginal sonography. Women with polycystic ovary syndrome, endocrine or metabolic abnormalities and women undergoing IVF with oocyte donation, will not be included. Ovarian reserve will be assessed by measuring the antral follicle count. Women with a predicted poor response or hyperresponse will be randomised for a standard versus an individualised FSH regime (150 IU/day, 225-450 IU/day and 100 IU/day, respectively). Participants will undergo a maximum of three stimulation cycles during maximally 18 months. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months after randomisation. Secondary outcomes are parameters for ovarian response, multiple pregnancies, number of cycles needed per live birth, total IU of FSH per stimulation cycle, and costs. All data will be analysed according to the intention-to-treat principle. Cost-effectiveness analysis will be performed to assess whether the health and associated economic benefits of individualised treatment of subfertile women outweigh the additional costs of an ORT.

Discussion

The results of this study will be integrated into a decision model that compares cost-effectiveness of the three dose-adjustment strategies to a standard dose strategy. The study outcomes will provide scientific foundation for national and international guidelines.

Trial registration

NTR2657

Keywords:
Ovarian reserve; Antral follicle count; IVF; Individualised FSH stimulation dosages; Live birth rate