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

Theodora C Van Tilborg,Jaap Friederich,Janet Kwee,Jan Peter De Bruin,Arie Verhoeff,Kathrin Fleischer,Fulco Van Der Veen,Annemieke Hoek,Ron J T Van Golde ,Petra A P Manger ,Frans M Helmerhorst ,Ben Willem J Mol ,M.h.a Van Hooff ,Walter K H Kuchenbecker ,Arne M Van Heusden ,G.j Scheffer ,Egbert A Brinkhuis ,Joop S.e Laven ,Carolien A.m Koks ,J.m.j Smeenk ,Cornelis B Lambalk ,Alexander V Sluijmer ,Harold R Verhoeve ,Helen L Torrance ,Marinus J.c Eijkemans ,Annemiek W Nap ,Frank J Broekmans

doi:10.1186/1472-6874-12-29

Abstract

BackgroundCosts 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/DesignMulticentre 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.DiscussionThe 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 registrationNTR2657

Highlights

Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH)
controlled ovarian hyperstimulation (COH) is an essential part of IVF which is needed to obtain a reasonable yield of oocytes which can be fertilised in vitro
The cohort will consist of 1,500 women screened for ovarian reserve by an antral follicle count (AFC) prior to IVF or intracytoplasmic sperm injection (ICSI) treatment

Summary

Introduction

Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH). Due to differences in ovarian reserve between women, ovarian response 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. This has never been confirmed in a large randomised controlled trial (RCT). In vitro fertilisation (IVF) is the treatment of last resort for many subfertile couples and a very costly one, partly due to the use of expensive drugs, i.e. gonadotrophins, needed for controlled ovarian hyperstimulation (COH) [1]. The result is that the poor responder may go through a series of treatment cycles with an overall poor prospect for pregnancy

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