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

Contains fulltext : 109739.pdf (publisher's version ) (Open Access)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

Let&rsquo;s get back to work: survival analysis on the return-to-work after depression

Pepijn Vemer,1 Clazien A Bouwmans,1 Moniek C Zijlstra-Vlasveld,2 Christina M van der Feltz-Cornelis,2&ndash;4 Leona Hakkaart-van Roijen1 1Institute for Medical Technology Assessment, Erasmus University Rotterdam, Rotterdam, 2Institute of Mental Health and Addiction (Trimbos-institute), Utrecht, 3Tilburg University, Tranzo, Academic Centre &#39;Geestdrift&#39;, Tilburg, 4Clinical Centre for Body, Mind and Health, Tilburg, The Netherlands Purpose: Absence from work due to mental disorders is substantial. Additionally, long-term absence from work is associated with a reduced probability of return-to-work (RTW). Major depressive disorder (MDD) is a prevalent condition in Dutch occupational health care settings. An early estimate of the prognosis regarding RTW in patients with MDD could serve both as a point of departure for the identification of high-risk cases and as an instrument to monitor the course of the disorder and of RTW. In the current study, we aimed to assess the added value of health-related quality of life (HRQoL) and severity of depression to predict the time to RTW. Patients and methods: Data were derived from a prospective longitudinal study aimed to evaluate the cost effectiveness of a collaborative care treatment in sick-listed workers with MDD. We included demographic, job-related, and health-related variables. Severity of depression was measured using the Patient Health Questionnaire Depression Scale-9 (PHQ-9). HRQoL was measured using two generic preference-based instruments, the EuroQol 5-Dimension (EQ-5D&trade;) and the Medical Outcomes Study Short Form Health Survey (SF-36). A survival model was constructed by applying different survival functions to assess the best fit for the data. Additionally, survival analyses were performed to assess the added value of the two HRQoL measures and depression severity for predicting RTW. Results: Females and older patients had a longer time to RTW. The same was true for patients with a full-time job and patients with more decision latitude. Patients in a management position and patients with more social support had a shorter time to RTW. Severity of depression was not predictive for the time to RTW. HRQoL measured by the SF-36 was a significant predictor for the time to RTW. Conclusion: HRQoL emerged as a significant predictor for the time to RTW. However, severity of depression was not predictive for the time to RTW. These results suggest the importance of assessing HRQoL in addition to severity of disease to assess functionality. Keywords: major depressive disorder, survival analyses, return-to-work, HRQo

The inSIGHT study: costs and effects of routine hysteroscopy prior to a first IVF treatment cycle. A randomised controlled trial.

Contains fulltext : 109856.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: In in vitro fertilization (IVF) and intracytoplasmatic sperm injection (ICSI) treatment a large drop is present between embryo transfer and occurrence of pregnancy. The implantation rate per embryo transferred is only 30%. Studies have shown that minor intrauterine abnormalities can be found in 11-45% of infertile women with a normal transvaginal sonography or hysterosalpingography. Two randomised controlled trials have indicated that detection and treatment of these abnormalities by office hysteroscopy after two failed IVF cycles leads to a 9-13% increase in pregnancy rate. Therefore, screening of all infertile women for intracavitary pathology prior to the start of IVF/ICSI is increasingly advocated. In absence of a scientific basis for such a policy, this study will assess the effects and costs of screening for and treatment of unsuspected intrauterine abnormalities by routine office hysteroscopy, with or without saline infusion sonography (SIS), prior to a first IVF/ICSI cycle. METHODS/DESIGN: Multicenter randomised controlled trial in asymptomatic subfertile women, indicated for a first IVF/ICSI treatment cycle, with normal findings at transvaginal sonography. Women with recurrent miscarriages, prior hysteroscopy treatment and intermenstrual blood loss will not be included. Participants will be randomised for a routine fertility work-up with additional (SIS and) hysteroscopy with on-the-spot-treatment of predefined intrauterine abnormalities versus the regular fertility work-up without additional diagnostic tests. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months of IVF/ICSI treatment after randomisation. Secondary study outcome parameters are the cumulative implantation rate; cumulative miscarriage rate; patient preference and patient tolerance of a SIS and hysteroscopy procedure. All data will be analysed according to the intention-to-treat principle, using univariate and multivariate logistic regression and cox regression. Cost-effectiveness analysis will be performed to evaluate the costs of the additional tests as routine procedure. In total 700 patients will be included in this study. DISCUSSION: The results of this study will help to clarify the significance of hysteroscopy prior to IVF treatment. TRIAL REGISTRATION: NCT01242852