The need for longitudinal data on the value of fertility treatment for infertile patients' quality of life: A review and pilot study.

Infertility threatens the life goal of parenthood and, hence, quality of life (QoL) of (wo)men, but the fertility clinic trajectory might be burdensome. This review of longitudinal studies and pilot longitudinal study examines the impact of the pre-in vitro fertilization (IVF) fertility clinic trajectory on patient-reported outcome measures (PROMs) for emotional well-being, including QoL. A publication found that the diagnostic workup decreases men's infertility-specific distress while publications disagree whether it decreases (wo)men's anxious and depressive reactions. Intrauterine insemination (IUI) was found to increase (wo)men's depressive reactions. Publications on infertility-specific, health-related, and overall QoL were missing. The pilot indicated that (wo)men's overall QoL is not affected by the diagnostic workup but is decreased by the time of the third IUI. Longitudinal studies on the impact of starting the fertility clinic trajectory on PROMs are needed as they are essential for patient-centered clinical decision-making and patient-centered policy-level decision-making.

Great expectations of IVF patients: the role of gender, dispositional optimism and shared IVF prognoses.

STUDY QUESTION: Which success rates do female and male IVF patients expect, what determines their expectations and do patients reconsider their expectations after receiving a personal IVF prognosis at the expense of anxious reactions? SUMMARY ANSWER: Female and male IVF patients have unrealistic high expectations which are positively associated with their dispositional optimism, and which are only reconsidered by patients receiving a less than average IVF prognosis, which leads to more anxious reactions in females. WHAT IS KNOWN ALREADY: Female patients undergoing IVF are known to have unrealistic expectations of the success of their own IVF cycle. The available evidence suggests women expect above average performance of their fertility clinic and (family) reproductive systems. The association of gender and personality trait dispositional optimism, with expectations of IVF success and the impact of providing couples with their IVF prognosis have not been studied previously. STUDY DESIGN, SIZE, DURATION: A total of 148 partnered individuals participated in this prospective survey at two separate points in treatment: following oocyte aspiration (T1) and embryo transfer (T2) (2019-2020, participation rate = 85%). At the time of embryo transfer, gynaecologists provided couples with their IVF prognosis, calculated with the Adapted van Loendersloot model. Women and their male partners completed questionnaires independently and immediately following oocyte aspiration and embryo transfer. PARTICIPANTS/MATERIALS, SETTING, METHODS: Dispositional optimism ('LOT-R' questionnaire) and expectations of IVF success (numerical rating scale) were assessed in eligible couples commencing a 2nd-6th IVF cycle on T1. Expectations of IVF success and anxiety ('Spielberger State-Anxiety Inventory') were (re)assessed on T2. The inter-partner correlation of expectations of IVF success was examined. Linear mixed models examined hypothesized determinants of expectations of IVF success (T1) and explored (determinants of) whether participants reconsidered their expectations after receiving their IVF prognosis (T1-T2) and whether couple's IVF prognosis was associated with anxious reactions (T2). MAIN RESULTS AND THE ROLE OF CHANCE: The mean of the IVF success rates expected by patients immediately after oocyte aspiration was 59.1% (±20.0), irrespective of gender (P = 0.077). Partners expectations of IVF success were moderately correlated (r = 0.483; P < 0.001). Expectations of IVF success were positively associated with the participant's dispositional optimism (P < 0.001) but were not associated with their partner's dispositional optimism, women's age and their previous (un)successful IVF experiences. Gynaecologists gave couples their calculated IVF prognosis ranging from 4.8% to 69.2% (mean = 30.9%) at the time of embryo transfer. Gender did not influence whether participants reconsidered their expectations after receiving their prognosis. In contrast to the subgroup (n = 78), who received at least an average IVF prognosis and that did not reconsider their expectations of IVF success, the subgroup (n = 70) receiving a below average IVF prognosis lowered their expectations of IVF success (interaction effect: P < 0.001) from 55% to 46%. A below average IVF prognosis was associated with anxious reactions in women but not in men (interaction effect: P = 0.011). LIMITATIONS, REASONS FOR CAUTION: The study design and sample size were more optimal for examining hypothesized determinants of patient's expectations of IVF success than for studying the impact of sharing prognoses with patients. Whether (reconsidering) expectations influences IVF discontinuation rates and achieved live birth rates has yet to be followed-up. WIDER IMPLICATIONS OF THE FINDINGS: Clinics are advised to offer patients the opportunity of receiving their IVF prognosis. Providing prognoses is in line with patient preferences and tempers the unrealistic high expectations of both partners in couples with a less than average prognosis. A sensitive communication style is indicated, as lower prognoses are associated with mild anxious reactions in women. STUDY FUNDING/COMPETING INTEREST(S): E.A.F.D. holds a postdoctoral fellowship of the Research Foundation-Flanders (12H9819N) and this study was funded by the Research Council of the KU Leuven (C14/18/106; project of J.V., K.P. and E.A.F.D.) and as an investigator sponsored study of K.P. and E.A.F.D. by Merck nv/sa Belgium, an affiliate of Merck KGaA, Darmstadt, Germany. The authors declare no conflict of interest related to this study. TRIAL REGISTRATION NUMBER: N/A.

Systematic development of a mobile preconception lifestyle programme for couples undergoing IVF: the PreLiFe-programme.

STUDY QUESTION: Can we develop a preconception lifestyle programme for couples undergoing IVF that is in line with their needs. SUMMARY ANSWER: A mobile preconception lifestyle programme was systematically developed based on expert opinion, literature and needs of IVF-patients. WHAT IS KNOWN ALREADY: A healthy lifestyle prior to conception is not only beneficial for the general health of couples, but evidence on its importance for their reproductive health and the health of their children is also emerging. So far, the vast majority of fertility clinics do not offer a lifestyle programme for couples undergoing IVF. Therefore, the present study aimed to develop a lifestyle programme for IVF-couples. STUDY DESIGN, SIZE, DURATION: The development of the PreLiFe-programme was guided by the steps of the Medical Research Council (MRC) framework for developing complex interventions, a systematic approach for developing theory- and evidence-based health promotion interventions. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: First, the evidence base on lifestyle programmes for IVF-couples was reviewed. Second, several iterations between an expert panel, the literature, and quantitative and qualitative data from IVF-patients identified the content, the format, behaviour change techniques and theory of the programme. Third, the PreLiFe-programme was produced and the expected process and outcomes of a randomized controlled trial assessing it were modelled. Finally, user tests among experts and patients and pilot tests among patients were conducted. MAIN RESULTS AND ROLE OF CHANCE: The finally developed PreLiFe-programme is a mobile application to be used autonomously by both partners of IVF-couples during the first year of IVF, in combination with motivational interviewing over the telephone every three months (i.e. blended care). The PreLiFe-programme provides advice and skills training on physical activity, diet and mindfulness based stress reduction and is in part tailored based on monitoring and tracking the lifestyle of patients. Based on the literature the expert panel considers it plausible that all three components contribute to IVF-success rates. The PreLiFe-programme is likely to be acceptable to patients as it meets the need of patients for lifestyle advice and treatment information. LIMITATIONS, REASON FOR CAUTION: The pilot in IVF-couples had a 3-month duration. The feasibility of the PreLiFe-programme in other infertile populations and/or upon longer use is yet to be examined. Whether the PreLiFe-programme effectively improves lifestyle and IVF-success rates is currently being examined in a trial randomizing heterosexual couples starting IVF to the PreLiFe-programme or an attention-control group for 12 months. WIDER IMPLICATIONS OF THE FINDINGS: If the PreLiFe-programme improves lifestyle and the chance of IVF-success, it will be a powerful tool and provide guidance for implementing lifestyle programmes in fertility clinics. STUDY FUNDING/COMPETING INTEREST(S): Funded by the Research Foundation Flanders (FWO-TBM (Applied Biomedical Research with a Primary Social finality); reference: T005417N). The authors have no conflict of interest to report. TRIAL REGISTRATION NUMBER: NCT03790449.

The experiences of women with breast cancer who undergo fertility preservation.

STUDY QUESTION: How do women, who have just been diagnosed with breast cancer, experience oocyte or embryo banking? SUMMARY ANSWER: Fertility preservation was a challenging yet welcome way to take action when confronted with breast cancer. WHAT IS KNOWN ALREADY: Fertility preservation for women with breast cancer is a way to safeguard future chances of having children. Women who have just been diagnosed with breast cancer report stress, as do women who have to undergo IVF treatment. How women experience the collision of these two stressfull events, has not yet been studied. STUDY DESIGN SIZE DURATION: We performed a multicenter qualitative study with a phenomenological approach including 21 women between March and July 2014. Women were recruited from two university-based fertility clinics. PARTICIPANTS/MATERIALS SETTING METHODS: Women with breast cancer who banked oocytes or embryos 1-15 months before study participation were eligible. We conducted in-depth, face-to-face interviews with 21 women, which was sufficient to reach data saturation. MAIN RESULTS AND THE ROLE OF CHANCE: The 21 women interviewed had a mean age of 32 years. Analysis of the 21 interviews revealed three main experiences: the burden of fertility preservation, the new identity of a fertility patient and coping with breast cancer through fertility preservation. LIMITATIONS REASONS FOR CAUTION: Interviewing women after, rather than during, fertility preservation might have induced recall bias. Translation of quotes was not carried out by a certified translator. WIDER IMPLICATIONS OF THE FINDINGS: The insights gained from this study of the experiences of women undergoing fertility preservation while being newly diagnosed with breast cancer could be used as a starting point for adapting the routine psychosocial care provided by fertility clinic staff. Future studies are necessary to investigate whether adapting routine psychosocial care improves women's wellbeing. STUDY FUNDING/COMPETING INTERESTS: None of the authors in this study declare potential conflicts of interest. The study was funded by the Center of Reproductive Medicine of the Academic Medical Center.

A systematic review and secondary analysis of two studies identifying demographic and medical characteristics determining patient-centeredness in endometriosis care as experienced by patients.

STUDY QUESTION: What are the patient-specific determinants associated with patient-centered endometriosis care as measured by the ENDOCARE questionnaire (ECQ)? SUMMARY ANSWER: 'Overall grade for endometriosis care', 'educational level', 'membership of a patient organization' and 'having seen other specialists for endometriosis complaints' are correlated with overall patient-centeredness scores (PCS). WHAT IS KNOWN ALREADY: Patient-centeredness of endometriosis care can be evaluated using the validated ECQ. The ECQ leads to an overall PCS and separate PCS for 10 dimensions of endometriosis care. Previously, educational level and quality of life scores were found to be associated with ECQ results. STUDY DESIGN SIZE DURATION: First, a systematic literature review was performed (PROSPERO registration number: CRD42020169872). MEDLINE, Cochrane CENTRAL and EMBASE databases were searched from inception to May 2020 for studies in any language reporting on the results of the ECQ in patients with endometriosis. Two studies were identified. From the two studies, all original data were merged. In total, data from 546 patients were available for analysis. Second, univariate and multivariate regression analyses were performed to identify determinants for patient-centeredness of endometriosis care. PARTICIPANTS/MATERIALS SETTING METHODS: The two included studies evaluated patient-centeredness in four endometriosis care centers in Belgium and the Netherlands. All participants had surgically proven endometriosis. Possible patient-specific determinants were selected from the demographic and medical questions from the first part of the ECQ. These determinants were evaluated using linear regression analysis and all possible determinants with a P > 0.2 in the univariate analysis were selected for stepwise multivariate analysis. Separate analyses were performed for overall PCS and each of the 10 dimensions. MAIN RESULTS AND THE ROLE OF CHANCE: The two included studies provided data from 546 patients. After adjustment for care center, multivariate analysis showed that a higher 'grade for endometriosis care' (B = 0.66), a 'lower educational level' (B = 0.50), 'being member of a patient organization' (B = 0.49) and 'having seen other specialists for endometriosis complaints' (B = 0.34) were independently associated with higher overall PCS (R 2 = 0.41). 'Grade for endometriosis care' was a determinant for all dimensions of endometriosis care. 'Having seen other specialists for endometriosis complaints' was positively associated with the care dimensions 'respect for patients' values, preferences and expressed needs', 'continuity and transition' and 'technical skills'. Members of a patient organization showed higher scores on the care dimensions 'emotional support and alleviation of fear and anxiety', 'continuity and transition' and 'endometriosis clinic staff'. Furthermore, we found that having a higher level of education is associated with lower scores in the care dimensions 'physical comfort', 'emotional support and alleviation of fear and anxiety' and 'involvement of significant other'. LIMITATIONS REASONS FOR CAUTION: These results delineate the patient-specific determinants of patient-centered care as measured using the Dutch ECQ. Whether results are generalizable to other countries should be investigated in an international study. This requires the ECQ to be validated in other languages first. WIDER IMPLICATIONS OF THE FINDINGS: The aforementioned determinants of patient-centered care are of value for studies benchmarking clinics for their patient-centeredness. In addition, they help clinicians to determine how to tailor their care to individual patients. At every visit, patients could be asked to grade the endometriosis care (on a scale of 0-10) to easily investigate patient-centeredness. When there is more time, women with endometriosis should be asked to complete the entire ECQ to investigate patient-centeredness in depth. STUDY FUNDING/COMPETING INTERESTS: The department of reproductive medicine (involving C.B.L. and V.M.) of the Amsterdam UMC, Vrije Universiteit Amsterdam has received several research and educational grants from Guerbet, Merck and Ferring. The authors have no conflict of interest related to this manuscript.

The stepwise development of an interactive web-based sex education programme for subfertile couples: the Pleasure & Pregnancy programme.

STUDY QUESTION: Can we develop a web-based sex education programme (programme running in a web browser) that addresses the needs of subfertile couples who are advised expectant management for at least 6 months? SUMMARY ANSWER: The 'Pleasure & Pregnancy' programme addresses couples' needs, is likely to improve couples' sexual functioning, and is subsequently hypothesised to improve the chance of natural pregnancy. WHAT IS KNOWN ALREADY: According to professional guidelines (e.g. the Netherlands and UK) couples with unexplained subfertility and a good chance of natural pregnancy, should be advised at least 6 months of expectant management. Adherence to expectant management is challenging as couples and gynaecologist prefer a more active approach. Targeting sexuality may be useful as subfertility is a risk factor for decreased sexual functioning. STUDY DESIGN, SIZE, DURATION: A novel programme was developed according to the three steps of the Medical Research Councils' (MRC) framework. First, relevant literature was explored. Second, an interdisciplinary expert panel developed a theory (based on a systematic literature review and patient interviews) on how the chance of natural conception can be improved. Third, the expected process and outcomes were modelled. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two licenced clinical sexologists, two gynaecologists, a clinical embryologist and two midwife-researchers, all from Belgium and the Netherlands, proposed components for the sex education programme. PubMed was searched systematically for randomised controlled trials (RCTs) evaluating the proposed components in different patient populations. The needs of 12 heterosexual Dutch or Belgian couples who were advised expectant management were explored with in-depth interviews. The content and delivery characteristics of the novel programme were described in detail with the aid of 'Intervention Taxonomy'. To model the outcomes, a protocol for an RCT was designed, registered and submitted for publication. MAIN RESULTS AND THE ROLE OF CHANCE: To help maintain or improve sexual functioning, mainly pleasure, and hence increase pregnancy rates, the web-based Pleasure & Pregnancy programme contains a combination of psychosexual education and couple communication, mindfulness and sensate focus exercises. Information on the biology of conception and interaction with fertility clinic staff and peers were added based on couples' needs to increase potential acceptability. LIMITATIONS AND REASON FOR CAUTION: This paper outlines the development phase of a sex education programme according to the MRC-framework. Whether the Pleasure & Pregnancy programme actually is acceptable, improves sexual functioning, increases pregnancy rates and is cost-effective remains to be determined. WIDER IMPLICATIONS OF THE FINDINGS: No previous interactive web-based sex education programme has aimed to increase the natural pregnancy rate of subfertile couples by targeting their sexual pleasure. The Pleasure & Pregnancy programme addresses couples' needs and its effect on sexual functioning and pregnancy rate is plausible but remains to be demonstrated by an RCT which is currently ongoing. STUDY FUNDING/COMPETING INTEREST(S): Funding was provided by The Netherlands Organisation for Health Research and Development (ZonMw), Flanders Research Foundation and the University of Amsterdam. C.B.L. is editor-in-chief of Human Reproductionbut was blinded to all parts of the peer review process. The remaining authors have no conflict of interest to report. TRIAL REGISTRATION NUMBER: Not applicable.

Towards more patient-centred endometriosis care: a cross-sectional survey using the ENDOCARE questionnaire.

STUDY QUESTION: What is the performance of the patient-centredness of endometriosis care in a secondary and a tertiary care setting and how can it be improved? SUMMARY ANSWER: Overall, patient-centredness was comparable in the two endometriosis care centres, but differed regarding 'physical comfort' and 'continuity and transition'; both centres can learn how to improve several of their targets from the other's strengths. WHAT IS KNOWN ALREADY: The ENDOCARE questionnaire (ECQ) is a validated questionnaire for assessing the important quality dimension 'patient-centredness'. Patient-centredness is associated with quality of life, although this should be explored further by larger-scale studies. STUDY DESIGN SIZE DURATION: A cross-sectional survey, relying on the ECQ, was performed (during 2015 and 2016) among 407 women with surgically diagnosed endometriosis. PARTICIPANTS/MATERIALS SETTING METHODS: This study was conducted in a secondary and a tertiary care centre in the Netherlands. A total of 209 Dutch-speaking women who had endometriosis surgery (2013-2014), completed the ECQ after a postal invitation and, if needed, postal reminders. The assessed outcomes were: overall patient-centredness, the patient-centredness for each of its 10 dimensions, and the patient-centred strengths and targets for improvement. Case-mix adjusted patient-centredness scores (PCS) were compared and strengths and targets for improvement were identified with a matrix modelling importance against experience. The need to improve the targets was quantified with quality impact indices. MAIN RESULTS AND THE ROLE OF CHANCE: No difference was demonstrated between the overall PCS of the secondary and tertiary centres (respectively: 4.8 and 4.5; P = 0.15). No difference was found in PCS per dimension between the two clinics except for the secondary care centre performing better regarding 'physical comfort' (respectively: 4.5 and 3.0; P = 0.01) and 'continuity and transition' (respectively: 6.0 and 4.2; P = 0.01). The two centres had nine targets for improvement in common. The secondary and tertiary centres, respectively, had five and seven additional centre-specific targets for improvement. Cross-centre learning is encouraged as 9 out the 12 additional centre-specific targets were strengths in the other centre. The main improvement targets were being able to contact the centre in case of emergency (both centres), the involvement of a significant other (secondary centre), diagnostic delay (secondary centre), personal follow-up (tertiary centre) and disclosing the level of competence of healthcare providers (tertiary centre). LIMITATIONS REASON FOR CAUTION: Responders did not differ from non-responders in their stage of endometriosis, educational level, rating of endometriosis care and degree to which their complaints are suppressed. Endometriosis is a chronic condition and patient-centredness might be experienced differently at other points of the endometriosis care trajectory. WIDER IMPLICATION OF THE FINDINGS: The ECQ is a useful tool to assess patient-centredness in both secondary and tertiary care centres. Further research should focus on how to improve endometriosis care. STUDY FUNDING/COMPETING INTERESTS: No external funding was used. V.M. and C.B.L. report grants from Guerbet, grants from Merck and grants from Ferring outside the submitted work. All authors declare that they have no competing interests concerning this publication.

Patient-centeredness and endometriosis: Definition, measurement, and current status.

The patient-centeredness of care is important for health care quality, especially because it was recently associated with health-related quality of life, which is increasingly being recognized as the ultimate outcome parameter of health care. Therefore, insight into the definition, measurement, and current status of the patient-centeredness of clinics is important for all health care professionals caring for patients with endometriosis. The definition of patient-centered endometriosis care is based on research into the most common preferences, needs, and values of patients with endometriosis and can be summarized in ten dimensions. One valid and reliable questionnaire exists, the ENDOCARE questionnaire, which allows measuring the patient-centeredness status of an endometriosis clinic. This questionnaire has been used to benchmark centers in different countries and has allowed the identification of ten targets for improving the patient-centeredness of endometriosis care. The next step would be to use the ENDOCARE questionnaire before and after an improvement project.

Broad support for regulating the clinical implementation of future reproductive techniques.

STUDY QUESTION: Do gynaecologists, infertile patients and the general public, consider that regulation of the clinical implementation of stem cell-based fertility treatments is required? SUMMARY ANSWER: There is broad support from gynaecologists, patients and the general public for regulating the clinical implementation of future stem cell-based fertility treatments. WHAT IS KNOWN ALREADY: There is debate on the need to regulate the clinical implementation of novel techniques. Regulation may hinder their swift adoption and delay benefits for patients, but may prevent the implementation of ineffective or harmful techniques. Stem cell-based fertility treatments, which involve creating oocytes or spermatozoa by manipulating stem cells, are likely to be implemented in clinical practice in the near future and will probably impact future generations as well as the current one. STUDY DESIGN, SIZE, DURATION: A cross-sectional survey was conducted among gynaecologists working in fertility clinics (n = 179), patients with severe infertility (n = 348) and a representative sample of the general public (n = 1250). The questionnaire was disseminated in the Netherlands in the winter of 2015-2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: The newly developed questionnaire was reviewed by experts and tested among the general public. The questionnaire assessed whether participants wanted each of nine potential negative consequences of the clinical implementation of stem cell-based fertility treatments to be regulated. In addition, the importance of all negative and positive potential consequences, the appropriate regulatory body and its need to consult with advisors from various backgrounds was questioned. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 958 respondents completed the questionnaire (response rate: 54%). A large majority of each participant group (>85%) wanted regulation, for at least one potential negative consequence of the clinical implementation of stem cell-based fertility treatments. The majority of all participant groups wanted regulation for serious health risks for intended parents, serious health risks for children and the disposal of human embryos. Regulation for out-of-pocket costs and the burden of treatment received little support. The majority of gynaecologists and the general public, but not the patients, requested regulation for the risk of minor congenital abnormalities, the success rates and the naturalness of treatments. Nevertheless, the majority of patients did consider the former two potential negative consequences important. The majority of all groups preferred a national bioethics committee as the regulatory body. This committee should consult with advisors from various backgrounds and should consider the broader context of potential consequences of the stem cell-based fertility treatments. LIMITATIONS, REASONS FOR CAUTION: This empirical study focuses on only three stakeholder groups. This study reports on the perspective of the majority and this is not per definition the morally right perspective. The transferability of our findings to other cultures and other techniques remains unclear. WIDER IMPLICATIONS OF THE FINDINGS: A national bioethics committee, consulting with advisors from various backgrounds, should regulate the clinical implementation of future stem cell-based fertility treatments. Whether this broad support for regulation applies to novel techniques from other fields of medicine should be examined. STUDY FUNDING/COMPETING INTEREST(S): The Young Academy of the Royal Netherlands Academy of Arts and Sciences. None of the authors has any conflict of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Patient-centered early pregnancy care: a systematic review of quantitative and qualitative studies on the perspectives of women and their partners.

BACKGROUND: Early pregnancy complications, defined as miscarriage, recurrent miscarriage or ectopic pregnancy, affect the physical and psychological well-being of intended parents. Research in this field so far has focused mainly on improving accuracy of diagnostic tests and safety and effectiveness of therapeutic management. An overview of aspects of care valued by women and/or their partners is missing. OBJECTIVE AND RATIONALE: This systematic review aims to provide an overview of aspects of care valued by women and/or their partners faced with early pregnancy complications and to identify potential targets for improvement in early pregnancy healthcare. SEARCH METHODS: We searched five electronic databases for empirical quantitative or qualitative studies on patients' perspectives of early pregnancy care in July 2017. We first identified aspects of early pregnancy care valued by women and/or their partners based on qualitative and quantitative data and organized these aspects of care according to the eight dimensions of patient-centered care. Second, we extracted the assessment of service quality from women and/or their partners on each of these aspects of care based on quantitative data. Third, we combined the findings on patients' values with the findings of service quality assessment to identify potential targets for improvement in five groups according to how likely these targets are to require improvement. OUTCOMES: The search yielded 6240 publications, of which 27 studies were eligible for inclusion in this review. All included studies focused on miscarriage or recurrent miscarriage care. We identified 24 valued aspects of care, which all covered the eight dimensions of patient-centered care. The most frequently reported valued aspect was 'being treated as an individual person experiencing a significant life event rather than a common condition'. Assessment of service quality from women and/or their partners was available for 13 of the 24 identified aspects of care. Quantitative studies all documented service quality as problematic for these 13 aspects of care. We thus identified 13 potential targets for improvement in the patient-centeredness of miscarriage and recurrent miscarriage care of which none were very likely, four were likely, six were unlikely and three were very unlikely, to require improvement. The four likely potential targets for improvement were 'Understandable information provision about the etiology of pregnancy', 'Staff discussing patients' distress', 'Informing patients on pregnancy loss in the presence of a friend or partner' and 'Staff performing follow-up phone calls to support their patients after a miscarriage'. WIDER IMPLICATIONS: It is important for clinicians to realize that women and their partners undergoing a miscarriage experience a significant live event and appreciate an individual approach. Future qualitative studies are needed to explore the identified potential targets for improvement of (recurrent) miscarriage care and to explore patients' perspectives in women suspected and treated for ectopic pregnancy.

The importance of genetic parenthood for infertile men and women.

STUDY QUESTION: Do men and women beginning to attend a fertility clinic prefer genetic over non-genetic parenthood? SUMMARY ANSWER: Nearly, all infertile men and women prefer genetic parenthood. WHAT IS KNOWN ALREADY: Clinicians assume that all infertile couples prefer genetic parenthood over non-genetic parenthood and, therefore, consider treatments with donor gametes an option of last resort. Previous studies of the desire for parenthood identified 30 motivations for genetic parenthood, and 51 motivations for which having a genetically related child is not strictly necessary but might be deemed required. The exact strength of the preference of infertile men and women for genetic parenthood remains unclear, as does the importance of the various motivations. STUDY DESIGN, SIZE, DURATION: A questionnaire was developed based on a literature review. It was assessed by professionals and pilot tested among patients. The coded paper-pencil questionnaire was disseminated among both partners of 201 heterosexual infertile couples after their first consultation at one of two Belgian fertility clinics between October 2015 and May 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: The survey addressed: (i) the preference for genetic parenthood for themselves and for their partner, (ii) the importance of 30 motivations for genetic parenthood and (iii) the importance of 51 other motivations for parenthood and whether these motivations require being the genetic parent of their child to be fulfilled. To simplify presentation of the results, all 81 motivations were grouped into reliable categories of motivations using psychometric analyses. MAIN RESULTS AND THE ROLE OF CHANCE: The survey was completed by 104 women and 91 men (response rate: 49%). Almost all respondents (98%) favored genetic over non-genetic parenthood for both their partner and themselves. One-third of the respondents stated they only wanted to parent their own genetically related child. Achieving genetic parenthood for their partner was considered significantly more important than achieving genetic parenthood for themselves. Within couples, men had a stronger preference for genetic parenthood (P = 0.004), but this was not significant after correction for educational level, which was significantly associated with the preference of both men and women. The 30 motivations for becoming a genetic parent clustered into 11 categories of which 'to experience a natural process' was deemed most important. The 51 motivations for becoming a parent for which having a genetically related child is not strictly necessary clustered into 14 categories of which 'to contribute to a child's well-being' and 'to experience the love of a child' were most important. Respondents deemed they would need to be the genetic parent of their child to fulfill nearly all their motivations for parenthood. LIMITATIONS REASONS FOR CAUTION: We included couples that visited the fertility clinic for the first time, and the preference for genetic parenthood might change throughout a fertility treatment trajectory. Moreover, what prospective parents expect to be important for their future well-being might not really define parents' well-being. WIDER IMPLICATIONS OF THE FINDINGS: The presumed preference of couples for genetic parenthood was confirmed. Resistance against using donor gametes is more likely among lower educated individuals. Researching whether non-genetic parents actually feel they cannot fulfill the 51 motivations for parenthood, could be a basis for developing patient information. STUDY FUNDING/COMPETING INTEREST(S): Funded by the Parkes Foundation, the University of Amsterdam and the Leuven University Hospital. No conflict of interest.

The acceptability of stem cell-based fertility treatments for different indications.

STUDY QUESTION: What is the acceptability of using stem cell-based fertility treatments (SCFT) for different indications according to gynaecologists and the general public? SUMMARY ANSWER: The majority of gynaecologists and the general public accept SCFT for the indications female or male infertility in young heterosexual couples, and female infertility in single women and same-sex couples. WHAT IS KNOWN ALREADY: SCFT could result in genetic parenthood for intended parents with indications that cannot be treated using currently available methods, such as being in a same-sex relationship or female post-menopausal age. It is unclear whether the acceptability of SCFT differs between indications for treatment and whether gynaecologists and the general public differ in their assessments. STUDY DESIGN SIZE, DURATION: In November 2015, a cross-sectional survey was disseminated among 179 gynaecologists and a panel of 1250 respondents comprising a representative sample of the Dutch general public. PARTICIPANTS/MATERIALS, SETTING, METHODS: The potential indications for future SCFT to achieve genetic parenthood were identified by literature review. A questionnaire was developed, reviewed by experts from different disciplines and tested among the general public. The questionnaire asked whether treating eight groups of intended parents with SCFT was acceptable or not. Regression analysis examined whether demographic characteristics influenced choices and whether the general public and gynaecologists differed in opinion. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 82 (46%) gynaecologists and 772 (62%) members of the general public completed the survey. The acceptability of using SCFT varied according to both gynaecologists and the general public between the eight groups of intended parents (P < 0.001). The majority of the Dutch general public accepts SCFT for six out of eight possible indications, namely female infertility in young heterosexual couples (94%), male infertility in young heterosexual couples (94%), unexplained infertility in young heterosexual couples (83%), female infertility in single women (69%), lesbian couples (68%) and gay couples (62%). The majority of gynaecologists also found treating these groups acceptable, except for the indication of unexplained infertility, which was only accepted by a minority of gynaecologists (43%). A minority of both the general public and gynaecologists accepted SCFT for fertile women who want a child that is genetically only her own (27 and 6%, respectively) and for female infertility in heterosexual couples in which the woman is over 50 years of age (17% and 26%, respectively). Attaching low importance to religion, having progressive political preferences, not having a university degree, having experienced infertility, being a woman, being older and not being of European ethnicity were positively associated with considering using SCFT acceptable for one or multiple indications. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: The generalizability of our findings to future decades or other countries might be limited as opinions about novel technologies change over time and might vary across cultures. Support among gynaecologists and the general public is interesting but not proof of ethical acceptability. WIDER IMPLICATIONS OF THE FINDINGS: Once proven safe and effective, fear of limited acceptability by the general public is unwarranted, and thus should not stop gynaecologists from offering SCFT to single infertile women and same-sex couples in addition to young infertile heterosexual couples. STUDY FUNDING AND COMPETING INTEREST(S): Funded by the Young Academy of the Royal Netherlands Academy of Arts and Sciences and the Universities of Amsterdam and Leuven. No conflict of interest to declare.

Development and validation of the FertiMed questionnaire assessing patients' experiences with hormonal fertility medication.

STUDY QUESTION: Can a valid and reliable questionnaire be developed to assess patients' experiences with all of the characteristics of hormonal fertility medication valued by them? SUMMARY ANSWER: The FertiMed questionnaire is a valid and reliable tool that assesses patients' experiences with all medication characteristics valued by them and that can be used for all hormonal fertility medications, irrespective of their route of administration. WHAT IS KNOWN ALREADY: Hormonal fertility medications cause emotional strain and differ in their dosage regime and route of administration, although they often have comparable effectiveness. Medication experiences of former patients would be informative for medication choices. A recent literature review showed that there is no trustworthy tool to compare patients' experiences of medications with differing routes of administration, regarding all medication characteristics which patients value. STUDY DESIGN, SIZE, DURATION: The items of the new FertiMed questionnaire were generated by literature review and 23 patient interviews. In 2013, 411 IVF-patients were asked to retrospectively complete the FertiMed questionnaire to assess 1 out of the 8 different medications used for ovarian stimulation, induction of pituitary quiescence, ovulation triggering or luteal support. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 276 patients (on average 35 per medication) from 2 university fertility clinics (Belgium, the Netherlands) completed the FertiMed questionnaire (67% response rate). The FertiMed questionnaire questioned whether items were valued by patients and whether these items were experienced while using the assessed medication. Hence, the final outcome 'Experiences with Valued Aspects Scores' (EVAS) combined importance and experience ratings. The content and face validity, reliability, feasibility and discriminative potential of the FertiMed questionnaire were tested and changes were made accordingly. MAIN RESULTS AND THE ROLE OF CHANCE: Patient interviews defined 51 items relevant to seven medication characteristics previously proved to be important to patients. Item analysis deleted 10 items. The combined results from the reliability and content validity analysis identified 10 characteristics instead of 7. The final FertiMed questionnaire was valid (Adapted Goodness of Fit Index = 0.95) and all but one characteristic ('ease of use: disturbance') could be assessed reliably (Cronbach's α > 0.60). The EVAS per characteristic differed between the medications inducing pituitary quiescence (P = 0.001). LIMITATIONS, REASON FOR CAUTION: As all eight medications prescribed in the recruiting clinics were questioned, sample sizes per medication were rather small for presenting EVAS per medication and for testing the discriminative potential of the FertiMed questionnaire. WIDER IMPLICATION OF THE FINDINGS: The FertiMed questionnaire can be used for all hormonal fertility medications to assess in a valid and reliable way whether patients experience what they value regarding 10 medication characteristics (e.g. side effects and ease of use). Future randomized controlled trials (RCT) comparing medications could include the FertiMed questionnaire as a Patient Reported Experience Measure (PREM). Insights from these RCTs could be used to develop evidence-based decision aids aiming to facilitate shared physician-patient medication choices. STUDY FUNDING/COMPETING INTERESTS: Funding was received from the University of Leuven and Amsterdam University Medical Centre. E.A.F.D. holds a postdoctoral fellowship of the Research Foundation of Flanders. T.D. was appointed Vice-President and Head Global Medical Affairs Fertility at Merck (Darmstadt, Germany) on 1 October 2015. The reported project was initiated and finished before this date. The other authors had no conflicts of interest to declare.

Couples with non-obstructive azoospermia are interested in future treatments with artificial gametes.

STUDY QUESTION: Would couples diagnosed with non-obstructive azoospermia (NOA) consider two future treatments with artificial gametes (AGs) as alternatives for testicular sperm extraction followed by ICSI (TESE-ICSI)? SUMMARY ANSWER: Most couples with NOA (89%) would opt for treatment with AGs before attempting TESE-ICSI and/or after failed TESE-ICSI. WHAT IS KNOWN ALREADY: Couples with NOA who undergo TESE-ICSI have a 25% chance of conceiving a child. Two future treatments that are being developed are 'ICSI with artificial sperm formed from somatic cells' (ICSI with AGs) and 'natural conception after autotransplantation of in vitro proliferated spermatogonial stem cells' (natural conception with AGs). It is unknown what treatment preferences patients have. STUDY DESIGN, SIZE, DURATION: A cross-sectional survey conducted in 2012-2013, addressing all 921 couples diagnosed with NOA and treated with TESE-ICSI in Dutch fertility clinics between 2007 and 2012. The coded questionnaires were sent by mail and followed up with two reminders. PARTICIPANTS/MATERIALS, SETTING, METHODS: We developed the questionnaire based on a literature review and previous qualitative interviews, and included treatment preference and the valuation of nine treatment characteristics. We assessed reliability of the questionnaires and calculated mean importance scores (MISs: 0-10) of each treatment characteristic. We assessed which patient and treatment characteristics were associated with a couple's hypothetical treatment preference using binominal regression. MAIN RESULTS AND THE ROLE OF CHANCE: The vast majority (89%) of the 494 responding couples (response rate: 54%) would potentially opt for AGs as a first and/or a last resort treatment option. More specifically, as a first treatment couples were likely (67%) to prefer natural conception with AGs over TESE-ICSI and less likely to prefer ICSI with AGs over TESE-ICSI (34%). After failed TESE-ICSI, the majority of couples (75%) would want to attempt ICSI with AGs as a last resort option. The most important characteristics of treatment were safety for children (MIS: 8.2), pregnancy rates (MIS: 7.7) and curing infertility (MIS: 6.8). Costs, burden, naturalness and technological sophistication were of about equal importance (MIS: 3.1-4.0). The majority of patients rated conception at home and moral acceptability as not important (MIS: 1.7 and 0.8, respectively), but the importance attributed to these variables did still affect patients' likeliness to opt for AGs. LIMITATIONS AND REASONS FOR CAUTION: Couples with NOA not opting for TESE-ICSI were not included and might have other perspectives. Couples' hypothetical choices for AGs might differ from their actual choices once data on the costs, safety and pregnancy rates become available from these new treatment options. WIDER IMPLICATIONS OF THE FINDINGS: The interest of couples with NOA in potential future treatments with AGs encourages further pre-clinical research. Priority setting for research and future decision-making on clinical application of AGs should take all characteristics important to patients into account. STUDY FUNDING/COMPETING INTERESTS: The authors report no financial or other conflict of interest relevant to the subject of this article.

Reproductive choices and outcomes after freezing oocytes for medical reasons: a follow-up study.

STUDY QUESTION: What reproductive choices do women make after they have cryopreserved oocytes for medical reasons? SUMMARY ANSWER: Women who had cryopreserved oocytes for medical reasons and tried to become pregnant, either attempted natural conception or resorted to assisted reproduction with fresh oocytes. WHAT IS KNOWN ALREADY: Women confronted with a risk of premature ovarian insufficiency, due to gonadotoxic therapy, ovarian surgery or genetic predisposition, have an indication to cryopreserve oocytes. Many of these women will retain ovarian function, thus will retain the possibility of natural conception. The added value of cryopreserved oocytes to reproductive outcomes is unknown as there is a lack of follow-up of women who have cryopreserved oocytes for medical reasons. STUDY DESIGN, SIZE AND DURATION: This follow-up study included a cohort of 85 women who cryopreserved their oocytes for medical reasons between 2009 and 2012. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Medical data from women who cryopreserved their oocytes at the Centre for Reproductive Medicine in the Academic Medical Centre in Amsterdam were extracted and self-report questionnaires were disseminated. The collected data considered demographics, outcomes of ovarian stimulation, fertility-threatening treatments, menstrual cycle changes, pregnancy attempts and outcomes and intended plans for the cryopreserved oocytes. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 68 women, followed up for an average 25.3 months, returned the questionnaire (response rate: 80%). None of the women had used her cryopreserved oocytes although 16 women had tried to conceive. Of these women, eight were trying to conceive naturally, five had conceived naturally within 2 months and three had conceived with assisted reproduction not requiring cryopreserved oocytes (two women with conventional IVF because of tubal pathology and endometriosis and one woman with IUI because of polycystic ovary syndrome). Three out of the eight pregnancies had resulted in live births, two resulted in miscarriages and three were ongoing. Most women (71%) intended to conceive with their cryopreserved oocytes as a last resource option. LIMITATIONS, REASONS FOR CAUTION: Transferability of our findings is challenged by the small sample but positively affected by our high response rate. As the time span between cryopreservation of oocytes and follow-up was short, follow-up of the cohort should be repeated in 2 years. WIDER IMPLICATIONS OF THE FINDINGS: After a mean follow-up of 2 years, none of the women with a medical reason to cryopreserve oocytes had used her oocytes. Women who were trying to conceive during follow-up were doing so without using their stored oocytes. It is unclear whether starting assisted reproduction while having cryopreserved oocytes is the most appropriate clinical decision. Our findings emphasize the relevance of taking the chances of natural conception into account in counselling women about cryopreservation of oocytes. STUDY FUNDING/COMPETING INTERESTS: This study was not externally funded. There are no conflicts of interest to declare.

Perspectives of infertile men on future stem cell treatments for nonobstructive azoospermia.

Concerns have been expressed about the rapid introduction of new fertility treatments into clinical practice. Patients' perspectives on new treatments and their introduction into clinical practice are unexplored. Two alternative treatments for testicular sperm extraction followed by intracytoplasmic sperm injection in men with nonobstructive azoospermia (NOA), the formation of artificial sperm and autotransplantation of in vitro proliferated spermatogonial stem cells, are in a preclinical phase of development. This study aimed to explore, prior to future clinical introduction, which treatment aspects are valued by NOA patients and would be taken into account in deciding to undergo these future treatment options. In-depth telephone interviews were conducted with 14 men with NOA. Interviews were transcribed, analysed with content analysis and data saturation was reached. Besides the obvious factors, success rates and safety, patients valued 'the intensity of the procedure', 'the treatments' resemblance to natural conception' and 'feeling cured'. Patients supported the development of these treatments and were eager to take part if such treatments would become available in the future. The patient's perspective on innovative treatments can (co)direct reproductive research. More research into the patients' perspectives on innovations and minimal thresholds to be met prior to their introduction into clinical practice is required.

Quality indicators for all dimensions of infertility care quality: consensus between professionals and patients.

STUDY QUESTION: What is the relative importance of the six dimensions of quality of care according to different stakeholders and can a quality indicator set address all six quality dimensions and incorporate the views from professionals working in different disciplines and from patients? SUMMARY ANSWER: Safety, effectiveness and patient centeredness were the most important quality dimensions. All six quality dimensions can be assessed with a set of 24 quality indicators, which is face valid and acceptable according to both professionals from different disciplines and patients. WHAT IS KNOWN ALREADY: To our knowledge, no study has weighted the relative importance of all quality dimensions to infertility care. Additionally, there are very few infertility care-specific quality indicators and no quality indicator set covers all six quality dimensions and incorporated the views of professionals and patients. STUDY DESIGN, SIZE AND DURATION: A three-round iterative Delphi survey including patients and professionals from four different fields, conducted in two European countries over the course of 2011 and 2012. PARTICIPANTS/MATERIALS, SETTINGS AND METHODS: Dutch and Belgian gynaecologists, embryologists, counsellors, nurses/midwifes and patients took part (n = 43 in round 1 and finally 30 in round 3). Respondents ranked the six quality dimensions twice for importance and their agreement was evaluated. Furthermore, in round 1, respondents gave suggestions, which were subsequently uniformly formulated as quality indicators. In rounds 2 and 3, respondents rated the quality indicators for preparedness to measure and for importance (relation to quality and prioritization for benchmarking). Providing feedback allowed selecting indicators based on consensus between stakeholder groups. Measurable indicators, important to all stakeholder groups, were selected for each quality dimension. MAIN RESULTS: All stakeholder groups and most individuals agreed that safety, effectiveness and patient centeredness were the most important quality dimensions. A total of 498 suggestions led to the development of 298 indicators. Professionals were sufficiently prepared to measure 204 of these indicators. Based on importance, 52 (7-15 per dimension; round 2) and finally 24 (4 per dimension; round 3) quality indicators were selected. LIMITATIONS, REASONS FOR CAUTION: The final quality indicator set does not cover the entire care process, but rather takes a 'sample' of each quality dimension. Although the quality indicators are face valid and acceptable, their psychometric characteristics need to be tested by further research. WIDER IMPLICATIONS OF THE FINDINGS: Quality management should focus on safety, effectiveness and patient centeredness of care. Clinics can use the quality indicator set to assess all quality dimensions of their care.

The ENDOCARE questionnaire guides European endometriosis clinics to improve the patient-centeredness of their care.

STUDY QUESTION: How patient-centered are two included specialized endometriosis clinics relative to each other and how can they improve the patient-centeredness of their care? SUMMARY ANSWER: The validated ENDOCARE questionnaire (ECQ) reliably concluded that the adjusted overall patient-centeredness did not differ between the clinics, that each clinic was significantly more patient-centered for 2 out of 10 dimensions of patient-centered endometriosis care and that clinics 1 and 2 had to improve 8 and 13 specific care aspects, respectively. WHAT IS KNOWN ALREADY: Patient-centered endometriosis care is essential to high-quality care and is defined by 10 dimensions. The ECQ was developed, validated and proved to be reliable in a European setting of self-reported endometriosis patients but had not yet been used at a clinic level for quality management. STUDY DESIGN, SIZE, DURATION: A cross-sectional survey was disseminated in 2011 to all 514 women diagnosed with endometriosis during a laparoscopy indicated for pain and/or infertility during a retrospective 2-year period (2009-2010) in two university clinics from two different European countries. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total 337 patients completed the ECQ (216 and 121 per clinic). Respondents had a mean age of 34.3 years. Three in four reported a surgical diagnosis of moderate or severe endometriosis and the majority reported surgical treatment by a multidisciplinary team. The ECQ assessed the 10 dimensions of patient-centeredness, more specifically whether the health-care performance, as perceived by patients, measured up to what is important to patients in general. MAIN RESULTS: The ECQ was completed by 337 respondents (response rate = 65.6%). Reliability and validity of the ECQ for use on clinic level were confirmed. Clinics did not differ in overall mean importance scores; importance rankings of the ECQ dimensions were almost identical. The overall patient-centeredness scores (PCS), adjusted for education level, did not discriminate between the clinics. However, the adjusted PCS for the dimensions 'clinic staff' and 'technical skills' were significantly better in clinic 1, whereas the dimensions 'physical comfort' and 'access to care' were significantly better in clinic 2. There were 8 (clinic 1) and 13 (clinic 2) targets identified for joint and cross-clinic improvement. LIMITATIONS, REASONS FOR CAUTION: Response rates were relatively high. Recall bias was the most important limitation and research in more clinics is needed to define the statistical discriminative value of the ECQ. WIDER IMPLICATIONS OF THE FINDINGS: European endometriosis clinics can use the validated ECQ for reliable assessment of their 'patient-centeredness', for comparison with others and for setting specific targets to improve the patient-centeredness of their endometriosis care, to plan interventions, and to evaluate their effectiveness. STUDY FUNDING/COMPETING INTEREST: This work was funded by KU Leuven and European Network of Endometriosis (ENE), supported by the European Commission (Public Health Executive Agency). No competing interests are declared.

Patients from across Europe have similar views on patient-centred care: an international multilingual qualitative study in infertility care.

BACKGROUND: International patient centredness concepts were suggested but never conceptualized from the patients' perspective. Previously, a literature review and a monolingual qualitative study defined 'patient-centred infertility care' (PCIC). The present study aimed to test whether patients from across Europe value the same aspects of infertility care. METHODS: An international multilingual focus group (FG) study with 48 European patients from fertility clinics in Austria, Spain, the UK and Belgium, with deductive content analysis. RESULTS: All specific care aspects important to participants from all countries could be allocated to the 10 dimensions of PCIC, each discussed in every FG, including: 'information provision', 'attitude of and relationship with staff', 'competence of clinic and staff', 'communication', 'patient involvement and privacy', 'emotional support', 'coordination and integration', 'continuity and transition', 'physical comfort' and 'accessibility'. Most specific care aspects (65%) were discussed in two or more countries and only a few new codes (11%) needed to be added to the previously published coding tree. Rankings from across Europe clearly showed that 'information provision' is a top priority. CONCLUSIONS: The PCIC-model is the first patient-centred care (PCC) model based on the patients' perspective to be validated in an international setting. Although health-care organization and performance differ, the similarities between countries in the infertile patients' perspective were striking, as were the similarities with PCC models from other clinical conditions. A non-condition specific international PCC model and a European instrument for the patient centredness of infertility care could be developed. European professionals can learn from each other on how to provide PCC.