Implementing targeted expectant management in fertility care using prognostic modelling: a cluster randomized trial with a multifaceted strategy.

STUDY QUESTION: What is the effectiveness of a multifaceted implementation strategy compared to usual care on improving the adherence to guideline recommendations on expectant management for couples with unexplained infertility? SUMMARY ANSWER: The multifaceted implementation strategy did not significantly increase adherence to guideline recommendations on expectant management compared to care as usual. WHAT IS KNOWN ALREADY: Intrauterine insemination (IUI) with or without ovarian hyperstimulation has no beneficial effect compared to no treatment for 6 months after the fertility work-up for couples with unexplained infertility and a good prognosis of natural conception. Therefore, various professionals and policy makers have advocated the use of prognostic profiles and expectant management in guideline recommendations. STUDY DESIGN, SIZE, DURATION: A cluster randomized controlled trial in 25 clinics in the Netherlands was conducted between March 2013 and May 2014. Clinics were randomized between the implementation strategy (intervention, n = 13) and care as usual (control, n = 12). The effect of the implementation strategy was evaluated by comparing baseline and effect measurement data. Data collection was retrospective and obtained from medical record research and a patient questionnaire. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 544 couples were included at baseline and 485 at the effect measurement (247 intervention group/238 control group). MAIN RESULTS AND THE ROLE OF CHANCE: Guideline adherence increased from 49 to 69% (OR 2.66; 95% CI 1.45-4.89) in the intervention group, and from 49 to 61% (OR 2.03; 95% CI 1.38-3.00) in the control group. Multilevel analysis with case-mix adjustment showed that the difference of 8% was not statistically significant (OR 1.31; 95% CI 0.67-2.59). The ongoing pregnancy rate within six months after fertility work-up did not significantly differ between intervention and control group (25% versus 27%: OR 0.72; 95% CI 0.40-1.27). LIMITATIONS REASONS FOR CAUTION: There is a possible selection bias, couples included in the study had a higher socio-economic status than non-responders. How this affects guideline adherence is unclear. Furthermore, when powering for this study we did not take into account the unexpected improvement of adherence in the control group. WIDER IMPLICATIONS OF THE FINDINGS: Generalization of our results to other countries with recommendations on expectant management might be questionable because barriers for expectant management can be very different in other countries. Furthermore, due to a large variation in improved adherence rate in the intervention group it will be interesting to further analyse the process of implementation in each clinic with a process evaluation on professionals and couples' exposure to and experiences with the strategy. STUDY FUNDING/COMPETING INTEREST(S): Supported by Netherlands Organisation for Health Research and Development (ZonMW, project number 171203005). No competing interests. TRIAL REGISTRATION NUMBER: Dutch trial Register, www.trialregister.nl NTR3405. TRIAL REGISTRATION DATE: 19 April 2012. DATE OF FIRST PATIENT'S ENROLMENT: 10 July 2012.

Prognostic profiles and the effectiveness of assisted conception: secondary analyses of individual patient data.

BACKGROUND: At present, it is unclear which treatment strategy is best for couples with unexplained or mild male subfertility. We hypothesized that the prognostic profile influences the effectiveness of assisted conception. We addressed this issue by analysing individual patient data (IPD) from randomized controlled trials (RCTs). METHODS: We performed an IPD analysis of published RCTs on treatment strategies for subfertile couples. Eligible studies were identified from Cochrane systematic reviews and we also searched Medline and EMBASE. The authors of RCTs that compared expectant management (EM), intracervical insemination (ICI), intrauterine insemination (IUI), all three with or without controlled ovarian stimulation (COS) and IVF in couples with unexplained or male subfertility, and had reported live birth or ongoing pregnancy as an outcome measure, were invited to share their data. For each individual patient the chance of natural conception was calculated with a validated prognostic model. We constructed prognosis-by-treatment curves and tested whether there was a significant interaction between treatment and prognosis. RESULTS: We acquired data from 8 RCTs, including 2550 couples. In three studies (n = 954) the more invasive treatment strategies tended to be less effective in couples with a high chance of natural conception but this difference did not reach statistical significance (P-value for interaction between prognosis and treatment outcome were 0.71, 0.31 and 0.19). In one study (n = 932 couples) the strategies with COS (ICI and IUI) led to higher pregnancy rates than unstimulated strategies (ICI 8% versus 15%, IUI 13% versus 22%), regardless of prognosis (P-value for interaction in all comparisons >0.5), but at the expense of a high twin rate in the COS strategies (ICI 6% versus 23% and IUI 3% versus 30%, respectively). In two studies (n = 373 couples), the more invasive treatment strategies tended to be more effective in couples with a good prognosis but this difference did not reach statistical significance (P-value for interaction: 0.38 and 0.68). In one study (n = 253 couples) the differential effect of prognosis on treatment effect was limited (P-value for interaction 0.52), perhaps because prognosis was incorporated in the inclusion criteria. The only study that compared EM with IVF included 38 couples, too small for a precise estimate. CONCLUSIONS: In this IPD analysis of couples with unexplained or male subfertility, we did not find a large differential effect of prognosis on the effectiveness of fertility treatment with IUI, COS or IVF.

Supportive care for women with recurrent miscarriage: a survey to quantify women's preferences.

BACKGROUND: Supportive care is regularly offered to women with recurrent miscarriages (RMs). Their preferences for supportive care in their next pregnancy have been identified by qualitative research. The aim of this study was to quantify these supportive care preferences and identify women's characteristics that are associated with a higher or lower need for supportive care in women with RM. METHODS: A questionnaire study was conducted in women with RMs (≥ 2 miscarriages) in three hospitals in the Netherlands. All women who received diagnostic work-up for RMs from January 2010 to December 2010 were sent a questionnaire. The questionnaire quantified supportive care options identified by a previous qualitative study. We next analysed associations between women's characteristics (age, ethnicity, education level, parity, pregnancy during questionnaire and time passed since last miscarriage) and their feelings about supportive care options to elucidate any differences between groups. RESULTS: Two hundred and sixty-six women were asked to participate in the study. In total, 174 women responded (response rate 65%) and 171 questionnaires were analysed. Women with RM preferred the following supportive care options for their next pregnancy: a plan with one doctor who shows understanding, takes them seriously, has knowledge of their obstetric history, listens to them, gives information about RM, shows empathy, informs on progress and enquires about emotional needs. Also, an ultrasound examination during symptoms, directly after a positive pregnancy test and every 2 weeks. Finally, if a miscarriage occurred, most women would prefer to talk to a medical or psychological professional afterwards. The majority of women expressed a low preference for admission to a hospital ward at the same gestational age as previous miscarriages and for bereavement therapy. The median preference, on a scale from 1 to 10, for supportive care was 8.0. Ethnicity, parity and pregnancy at the time of the survey were associated with different preferences, but female age, education level and time passed since the last miscarriage were not. CONCLUSIONS: Women with RM preferred a plan for the first trimester that involved one doctor, ultrasounds and the exercise of soft skills, like showing understanding, listening skills, awareness of obstetrical history and respect towards the patient and their miscarriage, by the health care professionals. In the event of a miscarriage, women prefer aftercare. Women from ethnic minorities and women who were not pregnant during the questionnaire investigation were the two patient groups who preferred the most supportive care options. Tailor-made supportive care can now be offered to women with RM.

The prognostic profile of subfertile couples and treatment outcome after expectant management, intrauterine insemination and in vitro fertilisation: a study protocol for the meta-analysis of individual patient data.

OBJECTIVE: The current evidence concerning the best treatment option for couples with unexplained and male subfertility is inconclusive. Most studies that have evaluated the effectiveness of treatment options, such as expectant management (EM), intrauterine insemination (IUI), with or without controlled ovarian stimulation (COS), and in vitro fertilisation (IVF), have not taken the couples' prognosis into account. It is very likely that the individual prognosis of the couple influences the effect of treatment. Individual patient data analyses allow us to take these prognostic factors into account, and to evaluate their effect on treatment outcome. This study aims to use anonymised data from relevant published trials to perform an individual patient data meta-analysis, evaluating the effect of couples' prognosis on the effectiveness of EM, IUI, with or without COS, and IVF. METHODS: Based on earlier systematic reviews and an updated search, randomised controlled trials will be considered for inclusion. Untreated subfertile couples with unexplained or male subfertility included in trials comparing EM, IUI, with or without COS, and IVF are included. Authors of the included studies will be invited to share their original anonymised data. The data will be assessed on validity, quality and completeness. The prognosis of the individual couple will be calculated with existing prognostic models. The effect of the prognosis on treatment outcome will be analysed with marker-by-treatment predictiveness curves, illustrating the effect of prognosis on treatment outcome. This study is registered in PROSPERO (registration number CRD42011001832). CONCLUSION: Ultimately, this study may help to select the appropriate fertility treatment, tailored to the needs of an individual couple.

Tailored expectant management: a nationwide survey to quantify patients' and professionals' barriers and facilitators.

BACKGROUND: Prognostic models for natural conception help to identify subfertile couples with high chances of natural conception, who do not need fertility treatment yet. The use of such models and subsequent tailored expectant management (TEM) is not always practiced. Previous qualitative research has identified barriers and facilitators of TEM among patients and professionals. The aim of this study was to assess the prevalence of those barriers and facilitators and to evaluate which factors predict patients' appreciation of TEM and professionals' adherence to TEM. METHODS: We performed a nationwide survey. Based on the previously identified barriers and facilitators two questionnaires were developed and sent to 195 couples and 167 professionals. Multivariate analysis was performed to evaluate which factors predicted patients' appreciation of TEM and professional adherence to TEM. RESULTS: In total, 118 (61%) couples and 117 (70%) professionals responded and 96 couples and 117 professionals were included in the analysis. Patients' mean appreciation of TEM was 5.7, on a 10-point Likert scale. Patients with a lower appreciation of TEM had a higher need for patient information (P = 0.047). The professionals reported a mean adherence to TEM of 63%. Adherence to TEM was higher when professionals were fertility doctors (P = 0.041). Facilitators in the clinical domain were associated with a higher adherence to TEM (P = 0.091). Barriers in the professional domain had a negative impact on adherence to TEM (P = 0.008). CONCLUSIONS: The limited implementation of TEM is caused by both patient and professional-related factors. This study provides practical tools to improve the implementation of TEM.

Accessing fertility treatment in New Zealand: a comparison of the clinical priority access criteria with a prediction model for couples with unexplained subfertility.

BACKGROUND: In New Zealand, public funding for assisted reproductive technology (ART) is restricted to subfertile women who are unlikely to conceive spontaneously, based on clinical and social criteria known as the clinical priority access criteria (CPAC) score. The objective of this study was to compare this CPAC score with a prediction model for predicting spontaneous conception, developed in the Netherlands (the Hunault model). METHODS: We performed a cohort study and included couples with unexplained subfertility and assessed the measure of agreement and the performance of the CPAC score and the Hunault prediction score. RESULTS: Of 663 couples referred, 249 (38%) couples had unexplained subfertility. Of 246 women with full follow-up data, there were 143 women (58%) who had a live birth during the follow-up period, 65 (26%) after fertility treatment and 78 (32%) after natural conception. There were 100 couples (41%) who had a Hunault prediction score of <30%, which is the Dutch treatment threshold, and 36 couples (15%) who had a CPAC score of >65, which is the New Zealand threshold for publically funded treatment. There were 69 couples (28%) who meet the threshold for treatment in the Netherlands but did not meet the New Zealand threshold for public funding. The kappa coefficient as a measure of agreement of the two scores and their treatment thresholds was 0.30, suggesting a fair agreement. The area under the curve for the CPAC and Hunault scores were both 0.63, but the Hunault model performed better in calibration. CONCLUSIONS: The CPAC score correlates fairly with the Hunault prediction score, although using the Hunault prediction model 26% more couples would be recommended for ART. The discriminative capacities of both scores were comparable, but the Hunault prediction score performed better in calibration. Funding models in New Zealand should consider treating those women with unexplained subfertility who are least likely to conceive spontaneously.

Patients' and professionals' barriers and facilitators of tailored expectant management in subfertile couples with a good prognosis of a natural conception.

BACKGROUND: European guidelines on fertility care emphasize that subfertile couples should receive information about their chances of a natural conception and should not be exposed to unnecessary treatments and risks. Prognostic models can help to estimate their chances and select couples with a good prognosis for tailored expectant management (TEM). Nevertheless, TEM is not always practiced. The aim of this study was to identify any barriers or facilitators for TEM among professionals and subfertile couples. METHODS: A qualitative study was performed with semi-structured in-depth interviews of 21 subfertile patients who were counselled for TEM and three focus-group interviews of 21 professionals in the field of reproductive medicine. Two theoretical models were used to guide the interviews and the analyses. The primary outcome was the set of identified barriers and facilitators which influence implementation of TEM. RESULTS: Among the subfertile couples, main barriers were a lack of confidence in natural conception, a perception that expectant management is a waste of time, inappropriate expectations prior to the first consultation, misunderstanding the reason for expectant management and overestimation of the success rates of treatment. Both couples and professionals saw the lack of patient information materials as a barrier. Among professionals, limited knowledge about prognostic models leading to a decision in favour of treatment was recognized as a main barrier. A main facilitator mentioned by the professionals was better management of patients' expectations. CONCLUSIONS: We identified several barriers and facilitators which can be addressed to improve the implementation of TEM. These should be taken into account when designing future implementation strategies.

Tailored expectant management: risk factors for non-adherence.

INTRODUCTION: Prediction models for spontaneous pregnancy are useful tools to prevent overtreatment, complications and costs in subfertile couples with a good prognosis. The use of such models and subsequent expectant management in couples with a good prognosis are recommended in the Dutch fertility guidelines, but not fully implemented. In this study, we assess risk factors for non-adherence to tailored expectant management. METHODS: Couples with mild male, unexplained and cervical subfertility were included in this multicentre prospective cohort study. If the probability of spontaneous pregnancy within 12 months was ≥40%, expectant management for 6-12 months was advised. Multivariable logistic regression was used to identify patient and clinical characteristics associated with non-adherence to tailored expectant management. RESULTS: We included 3021 couples of whom 1130 (38%) had a ≥40% probability of a spontaneous pregnancy. Follow-up was available for 1020 (90%) couples of whom 214 (21%) had started treatment between 6 and 12 months and 153 (15%) within 6 months. A higher female age and a longer duration of subfertility were associated with treatment within 6 months (OR: 1.06, 95% CI: 1.01-1.1; OR: 1.4; 95% CI: 1.1-1.8). A fertility doctor in a clinical team reduced the risk of treatment within 6 months (OR: 0.62; 95% CI: 0.39-0.99). CONCLUSIONS: In couples with a favorable prognosis for spontaneous pregnancy, there is considerable overtreatment, especially if the woman is older and duration of the subfertility is longer. The presence of a fertility doctor in a clinic may prevent early treatment.