Treatment effect of oil-based contrast is related to experienced pain at HSG : a post-hoc analysis of the randomised H2Oil study

The H2Oil study was an investigator-initiated study that was funded by our own academic institutions (AMC and VUmc) of the Amsterdam UMC. The funders had no role in study design, collection, analysis and interpretation of the data.Peer reviewedPublisher PD

The long-term costs and effects of tubal flushing with oil-based versus water-based contrast during hysterosalpingography

Acknowledgements The authors would like to thank all the participating women, the hospitals and their staff, the research nurses and the staff of the Nationwide Consortium for Women's Health Research (NVOG Consortium; www.zorgevaluatienederland.nl ) for logistical support. Thanks also go to the H2Oil study group collaborators: Nan van Geloven, Jos W. R. Twisk, Peter M. van de Ven and Peter G. A. Hompes for their contributions to this study. The original H2Oil RCT was an investigator-initiated study that was funded by the two academic institutions (AMC and VUmc) of the Amsterdam UMC. The long-term follow-up study and economic analysis, both investigator-initiated studies, were funded by a research grant from Guerbet, France. The funders had no role in study design or collection, analysis or interpretation of the data. Declaration of interest: C.T.P. has received consultancy fees for external work from Guerbet, France. K.D. reports receiving travel and speakers fee from Guerbet. H.R.V. reports receiving consultancy fees from Ferring. M.G. works at the Department of Reproductive Medicine of the Amsterdam UMC (location AMC and location VUmc). Location VUmc has received several research and educational grants from Guerbet, Merck and Ferring. C.B.L. reports speakers fee from Ferring in the past, and his department receives research grants from Ferring, Merck and Guerbet. V.M. reports receiving travel and speakers fees as well as research grants from Guerbet. B.W.J.M. is supported by a NHMRC Investigator grant (GNT1176437). B.W.J.M. has received research grants from Merck and Guerbet. The other authors report no financial or commercial conflicts of interest.Peer reviewedPublisher PD

Cumulative live birth rates in low-prognosis women

No external funds were obtained for the present study. The OPTIMIST study was funded by The Netherlands Organization for Health Research and Development (ZonMW number 171102020).Peer reviewedPublisher PD

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

Bone loss and the aromatase inhibitors

The increasing use of systemic adjuvant therapies has considerably improved the prognosis from early breast cancer. However, some of these therapies affect bone metabolism, resulting in osteoporosis. Aromatase inhibitors lower circulating oestrogen levels to almost unrecordable levels in postmenopausal women, predisposing them to bone loss with an increase in fracture risk. Ongoing clinical trials are favouring the use of the aromatase inhibitors over tamoxifen and this may advocate greater use of these drugs in the future. Strategies for the identification and management of treatment-induced bone loss are currently being defined

Individualized versus standard FSH dosing in women starting IVF/ICSI:An RCT. Part 1: The predicted poor responder

STUDY QUESTION: Does an increased FSH dose result in higher cumulative live birth rates in women with a predicted poor ovarian response, apparent from a low antral follicle count (AFC), scheduled for IVF or ICSI? SUMMARY ANSWER: In women with a predicted poor ovarian response (AFC <11) undergoing IVF/ICSI, an increased FSH dose (225/450 IU/day) does not improve cumulative live birth rates as compared to a standard dose (150 IU/day). WHAT IS KNOWN ALREADY: In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can predict ovarian response to stimulation. The FSH starting dose is often adjusted based on the ORT from the belief that it will improve live birth rates. However, the existing RCTs on this topic, most of which show no benefit, are underpowered. STUDY DESIGN, SIZE, DURATION: Between May 2011 and May 2014, we performed an open-label multicentre RCT in women with an AFC <11 (Dutch Trial Register NTR2657). The primary outcome was ongoing pregnancy achieved within 18 months after randomization and resulting in a live birth. We needed 300 women to assess whether an increased dose strategy would increase the cumulative live birth rate from 25 to 40% (two-sided alpha-error 0.05, power 80%). PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with an AFC ≤ 7 were randomized to an FSH dose of 450 IU/day or 150 IU/day, and women with an AFC 8–10 were randomized to 225 IU or 150 IU/day. In the standard group, dose adjustment was allowed in subsequent cycles based on pre-specified criteria. Both effectiveness and cost-effectiveness of the strategies were evaluated from an intention-to-treat perspective. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 511 women were randomized, 234 with an AFC ≤ 7 and 277 with an AFC 8–10. The cumulative live birth rate for increased versus standard dosing was 42.4% (106/250) versus 44.8% (117/261), respectively [relative risk (RR): 0.95 (95%CI, 0.78–1.15), P = 0.58]. As an increased dose strategy was more expensive [delta costs/woman: €1099 (95%CI, 562–1591)], standard FSH dosing was the dominant strategy in our economic analysis. LIMITATIONS, REASONS FOR CAUTION: Despite our training programme, the AFC might have suffered from inter-observer variation. As this open study permitted small dose adjustments between cycles, potential selective cancelling of cycles in women treated with 150 IU could have influenced the cumulative results. However, since first cycle live birth rates point in the same direction we consider it unlikely that the open design masked a potential benefit for the individualized strategy. WIDER IMPLICATIONS OF THE FINDINGS: Since an increased dose in women scheduled for IVF/ICSI with a predicted poor response (AFC <11) does not improve live birth rates and is more expensive, we recommend using a standard dose of 150 IU/day in these women