Puberty progression in girls with Turner syndrome after ovarian tissue cryopreservation.

OBJECTIVE: To study the impact of unilateral ovariectomy for ovarian tissue cryopreservation (OTC) on the function of the remaining ovary in girls with Turner syndrome. DESIGN: A prospective cohort study as follow up of OTC in a research setting (The TurnerFertility trial, NCT03381300). SETTING: University hospital in Nijmegen, the Netherlands. SUBJECTS: A total of 28 girls with Turner syndrome with follicles in their cryopreserved ovarian cortex tissue, aged 5-19 years. Of the 28 girls, 21 girls had a 45,X/46,XX mosaic karyotype, five had structural aberrations of the X-chromosome, one girl had a 45,X monosomy, and one girl had a 45,X/47,XXX karyotype. INTERVENTIONS: Girls were monitored annually after OTC for pubertal development and levels of anti-Müllerian hormone (AMH), Follicle Stimulating Hormone, Luteinizing Hormone, Estradiol, and Inhibin B. MAIN OUTCOME MEASURES: Thelarche, menarche and onset of premature ovarian insufficiency. RESULTS: The girls were monitored for a median duration of 3.4 years (maximum 6.6 years). The pubertal development of five prepubertal girls is still unknown, all were under the age of 10 and had low gonadotropins and estradiol levels at the end of the follow-up. Seven of the eight girls around pubertal age (10-12 years) experienced spontaneous thelarche, while one received medication to induce puberty. Eleven of the fourteen girls between the age of 14-17 years experienced spontaneous menarche, three other girls with thelarche still had ongoing puberty at the end of follow-up with normal gonadotropins and AMH levels above the detection limit. Around six to twelve months after OTC, a decline in AMH concentration was observed in 57% of girls (16/28 girls), followed by an increase in AMH concentration in the following years. Six of the total 28 girls started hormone replacement therapy due to symptoms of premature ovarian insufficiency, and all had AMH levels below 0.50 µg/L before OTC. CONCLUSION: Pubertal development progressed after unilateral ovariectomy for OTC in most girls with Turner syndrome. Hormone replacement therapy was required within a few years for girls with unfavorable parameters before OTC, such as AMH below 0.50 µg/L. Decisions regarding OTC should be personalized, considering the girl's preferences and specific characteristics.

Cumulative live birth rate of a blastocyst versus cleavage stage embryo transfer policy during in vitro fertilisation in women with a good prognosis: multicentre randomised controlled trial.

OBJECTIVES: To evaluate whether embryo transfers at blastocyst stage improve the cumulative live birth rate after oocyte retrieval, including both fresh and frozen-thawed transfers, and whether the risk of obstetric and perinatal complications is increased compared with cleavage stage embryo transfers during in vitro fertilisation (IVF) treatment. DESIGN: Multicentre randomised controlled trial. SETTING: 21 hospitals and clinics in the Netherlands, 18 August 2018 to 17 December 2021. PARTICIPANTS: 1202 women with at least four embryos available on day 2 after oocyte retrieval were randomly assigned to either blastocyst stage embryo transfer (n=603) or cleavage stage embryo transfer (n=599). INTERVENTIONS: In the blastocyst group and cleavage group, embryo transfers were performed on day 5 and day 3, respectively, after oocyte retrieval, followed by cryopreservation of surplus embryos. Analysis was on an intention-to-treat basis, with secondary analyses as per protocol. MAIN OUTCOME MEASURES: The primary outcome was the cumulative live birth rate per oocyte retrieval, including results of all frozen-thawed embryo transfers within a year after randomisation. Secondary outcomes included cumulative rates of pregnancy, pregnancy loss, and live birth after fresh embryo transfer, number of embryo transfers needed, number of frozen embryos, and obstetric and perinatal outcomes. RESULTS: The cumulative live birth rate did not differ between the blastocyst group and cleavage group (58.9% (355 of 603) v 58.4% (350 of 599; risk ratio 1.01, 95% confidence interval (CI) 0.84 to 1.22). The blastocyst group showed a higher live birth rate after fresh embryo transfer (1.26, 1.00 to 1.58), lower cumulative pregnancy loss rate (0.68, 0.51 to 0.89), and lower mean number of embryo transfers needed to result in a live birth (1.55 v 1.82; P<0.001). The incidence of moderate preterm birth (32 to <37 weeks) in singletons was higher in the blastocyst group (1.87, 1.05 to 3.34). CONCLUSION: Blastocyst stage embryo transfers resulted in a similar cumulative live birth rate to cleavage stage embryo transfers in women with at least four embryos available during IVF treatment. TRIAL REGISTRATION: International Clinical Trial Registry Platform NTR7034.

Unravelling clinicians' shared decision-making adoption: a qualitative exploration through the lens of diffusion of innovations theory.

OBJECTIVES: This study uses the diffusion of innovations (DOI) theory to comprehensively understand the adoption of shared decision-making (SDM) in clinical practice, specifically focusing on the 'knowledge' and 'persuasion' stages within DOI. We aim to understand the challenges and dynamics associated with SDM adoption, offering insights for more patient-centred decision-making in healthcare. DESIGN: This qualitative study employs a modified framework analysis approach, integrating ethnographic and interview data from prior research, along with additional interviews. The framework used is based on the DOI theory. STUDY SETTING AND PARTICIPANTS: This study was conducted in the obstetrics and gynaecology department of a tertiary teaching hospital in the Eastern region of the Netherlands. It included interviews with 20 participants, including gynaecologists, obstetrics registrars and junior doctors currently practising in the department. Additionally, data from prior research conducted within the same department were incorporated, ensuring the maintenance of contextual consistency. RESULTS: Findings reveal a complex interplay between SDM's benefits and challenges. Clinicians value SDM for upholding patient autonomy and enhancing medical practice, viewing it as valuable for medical decision-making. Decision aids are seen as advantageous in supporting treatment decisions. Challenges include compatibility issues between patient and clinician preferences, perceptions of SDM as time-consuming and difficult and limitations imposed by the rapid pace of healthcare and its swift decisions. Additionally, perceived complexity varies by situation, influenced by colleagues' attitudes, with limited trialability and sparsely observed instances of SDM. CONCLUSIONS: Clinicians' decision to adopt or reject SDM is multifaceted, shaped by beliefs, cognitive processes and contextual challenges. Cognitive dissonance is critical as clinicians reconcile their existing practices with the adoption of SDM. Practical strategies such as practice assessments, open discussions about SDM's utility and reflective practice through professional development initiatives empower clinicians to make the best informed decision to adopt or reject SDM.

Towards reducing diagnostic delay in endometriosis in primary care: a qualitative study.

BACKGROUND: Due to a heterogeneity of symptoms, a lack of an adequate diagnostic test, and a lack of awareness, diagnostic delay in endometriosis in primary care on average amounts to 35 months. AIM: To determine which interventions are most feasible to reduce time to diagnosis in primary care, focusing on GPs' preferences, the intervention's content, design, and implementation. DESIGN & SETTING: We conducted a qualitative study by performing focus groups with GPs and GP trainees between July and October 2021. METHOD: Data collection was continued until saturation was obtained. Focus groups were transcribed and openly encoded. Themes were formulated by three independent researchers. RESULTS: Divided over five focus groups 22 GPs and 13 GP trainees participated. Three themes were formulated: increasing awareness, combined intervention, and reaching unaware GPs. Suggestions for a combined intervention strategy were adaptation of guidelines, a diagnostic support tool, and compulsory education. To reach unaware GPs, participants felt that education should be offered in regional networks and education for GP trainees should be mandatory. A guideline on menstrual symptoms should be considered and the term endometriosis should be added to the differential diagnosis paragraphs of existing guidelines. A diagnostic support tool should be linked to a guideline and consist of a flowchart with steps starting with the first presentation of symptoms leading to the diagnosis of endometriosis. CONCLUSION: According to GPs, a combined intervention strategy consisting of an adapted guideline, a diagnostic support tool, and education might be successful interventions in reducing diagnostic delay in endometriosis.

Navigating fertility dilemmas across the lifespan in girls with Turner syndrome-a scoping review.

BACKGROUND: Girls with Turner syndrome (TS) lack a partial or complete sex chromosome, which causes an accelerated decline of their ovarian reserve. Girls have to deal with several dilemmas related to their fertility, while only a limited number of them are referred to a fertility specialist and counselled about options of family planning on time. OBJECTIVE AND RATIONALE: This scoping review provides an update of the literature on fertility in girls with TS throughout their lifespan and aims to propose a clinical practice guideline on fertility in TS. SEARCH METHODS: Databases of PubMed, Embase, and Web of science were searched using the following key terms: Turner syndrome, fertility, puberty, pregnancy, sex-hormones, karyotype, fertility preservation, assisted reproductive techniques, and counselling, alongside relevant subject headings and synonymous terms. English language articles published since 2007 were critically reviewed. Pregnancies after using donated oocytes and data about girls with TS with Y-chromosomal content were excluded. OUTCOMES: This search identified 1269 studies of which 120 were extracted for the review. The prevalence of natural conception ranged from 15% to 48% in women with 45,X/46,XX, 1% to 3% in women with 45,X, and 4% to 9% in women with other TS karyotypes. When assessing a girl's fertility potential, it was crucial to determine the karyotype in two cell lines, because hidden mosaicism may exist. In addition to karyotype, assessment of anti-Müllerian hormone (AMH) played a significant role in estimating ovarian function. Girls with AMH above the detection limit were most likely to experience spontaneous thelarche, menarche, and ongoing ovarian function during the reproductive lifespan. Fertility preservation became more routine practice: vitrification of oocytes was reported in 58 girls with TS and a median of five oocytes were preserved per stimulation. Ovarian tissue cryopreservation has demonstrated the presence of follicles in approximately 30% of girls with TS, mostly in girls with mosaic-TS, spontaneous puberty, and AMH above the detection limit. Although girls and their parents appreciated receiving counselling on fertility in TS, only one in ten girls with TS received specialized counselling. Unfamiliarity with fertility preservation techniques or uncertainties regarding the eligibility of a girl for fertility preservation constituted barriers for healthcare professionals when discussing fertility with girls with TS. WIDER IMPLICATIONS: There currently is a high demand for fertility preservation techniques in girls with TS. A reliable prognostic model to determine which girls with TS might benefit from fertility preservation is lacking. Only a minority of these girls received comprehensive fertility counselling on the full spectrum of fertility, including uncertainties of fertility preservation, pregnancy risks, and alternatives, such as adoption. Fertility preservation could be a viable option for girls with TS. However, the question remains whether enough oocytes can be obtained for a realistic prospect of a live birth. It is important that girls and parents are empowered with the necessary information to make a well-informed decision.

Assessing the educational quality of shared decision-making interventions for residents: A systematic review.

OBJECTIVES: Many studies on educational interventions to enhance residents' shared decision-making (SDM) skills show limited improvement in SDM skills and clinical outcomes. One plausible explanation for these suboptimal results is the insufficient emphasis on the educational quality of training interventions. METHODS: This review evaluates interventions' educational quality using an evaluation framework based on a previous study on effective skills transfer and a well-known SDM model. A systematic review was conducted, searching three databases until December 13, 2022. We assessed study quality by calculating MERSQI scores, examined the levels of study effects based on Kirkpatrick's model, and applied our evaluation framework to assess the interventions' educational quality. Given the heterogeneity among the studies, a meta-analysis was not feasible. RESULTS: Twenty-six studies were included. Role-play and feedback were common training characteristics (65% and 54% of interventions). Only four studies (15%) met our framework's high educational quality threshold. No correlation was found between MERSQI scores and educational quality. CONCLUSIONS: This review is a valuable attempt to assess the educational quality of SDM interventions beyond measuring study outcomes. PRACTICE IMPLICATIONS: Future evaluation frameworks should consider study results, training characteristics, and training content. Our framework offers a sound basis for such an evaluation framework.

Reproductive Outcomes of Women with Turner Syndrome Undergoing Oocyte Vitrification: A Retrospective Multicenter Cohort Study.

BACKGROUND: Turner syndrome (TS) is accompanied with premature ovarian insufficiency. Oocyte vitrification is an established method to preserve fertility. However, data on the oocyte yield in women with TS who vitrify their oocytes and the return rate to utilize the oocytes are scarce. METHODS: Retrospective multicenter cohort study. Data was collected from medical records of women with TS who started oocyte vitrification between 2010 and 2021. RESULTS: Thirty-three women were included. The median cumulative number of vitrified oocytes was 20 per woman. Complications occurred in 4% of the cycles. Significant correlations were found between the cumulative number of vitrified oocytes and AMH (r = 0.54 and p < 0.01), AFC (r = 0.49 and p < 0.01), percentage of 46,XX cells (r = 0.49 and p < 0.01), and FSH (r = -0.65 and p < 0.01). Spontaneous (n = 8) and IVF (n = 2) pregnancies occurred in 10 women ± three years after vitrification. So far, none of the women have returned to utilize their vitrified oocytes. CONCLUSIONS: Oocyte vitrification is a feasible fertility preservation option for women with TS, particularly in those with 46,XX cell lines or sufficient ovarian reserve. Multiple stimulation cycles are recommended to reach an adequate number of vitrified oocytes for pregnancy. It is too early to draw conclusions about the utilization of vitrified oocytes in women with TS.

Is it fun or is it hard? Studying physician-related attributes of shared decision-making by ranking case vignettes.

Objective: This study investigated provider-related attributes of shared decision-making (SDM). It studied how physicians rank SDM cases compared to other cases, taking 'job satisfaction' and 'complexity' as ranking criteria. Methods: Ten vignettes representing three cases of SDM, three cases dealing with patients' emotions and four with technical problems were designed to conduct a modified ordinal preference elicitation study. Gynaecologists and trainees ranked the vignettes for 'job satisfaction' or 'complexity'. Results were analysed by comparing the top three and down three ranked cases for each type of case using exact p-values obtained with custom-made randomisation tests. Results: Participants experienced more satisfaction significantly from performing technical cases than cases dealing with emotions or SDM. Moreover, technical cases were perceived as less complex than those dealing with emotions. However, results were inconclusive about whether gynaecologists find SDM complex. Conclusion: Findings suggest gynaecologists experience lower satisfaction with SDM tasks, possibly due to them falling outside their comfort zone. Integrating SDM into daily routines and promoting culture change favouring dealing with non-technical problems might help mitigate issues in SDM implementation. Innovation: Our novel study assesses SDM in the context of task appraisal, illuminating the psychology of health professionals and providing valuable insights for implementation science.

TurnerFertility trial: fertility preservation in young girls with Turner syndrome by freezing ovarian cortex tissue-a prospective intervention study.

OBJECTIVE: To evaluate which girls with Turner syndrome (TS) could benefit from fertility preservation by ovarian tissue cryopreservation on the basis of karyotype, puberty status, and hormonal data. DESIGN: Prospective intervention study; participants were included between 2018 and 2020. SETTING: Tertiary hospital in the Netherlands. PATIENTS: In total, 106 girls with TS aged between 2 and 18 years were included. Girls with minor X chromosome deletions, Y chromosomal content, active infections, or contraindications for surgery were excluded. INTERVENTION: A laparoscopic unilateral ovariectomy was performed to obtain ovarian cortical tissue for cryopreservation. One tissue fragment per participant was used to determine the number of follicles per ovary by serial sectioning and staining. Chromosome analysis was performed on lymphocytes and buccal cells. A blood sample was taken before the ovariectomy for hormonal analysis. MAIN OUTCOME MEASURES: The presence of follicles in ovarian cortex tissue from girls with TS in relation to karyotype, puberty status, and hormonal data. RESULTS: A unilateral ovariectomy was performed on 93 girls with TS. Complications after surgery occurred in 5 girls, including luxation of psychological symptoms in 2 girls. In 13 (14%) girls, a 46,XX cell line was found in buccal cells that was absent in lymphocytes. Follicles were observed in 30 (32%) of the 93 girls and were found mainly in girls with a 46,XX cell line in lymphocytes or buccal cells (Phi coefficient = 0.55). Spontaneous onset of puberty (Phi coefficient = 0.59), antimüllerian hormone (AMH; point-biserial correlation [r] = 0.82), inhibin B (r = 0.67), and follicle-stimulating hormone (r = -0.46) levels were also correlated strongly with the presence of follicles. Furthermore, AMH levels had a significant correlation with the number of follicles per ovary (r = 0.66). CONCLUSION: Favorable predictive markers for the presence of follicles included either a 46,XX cell line, spontaneous onset of puberty, or a combination of measurable AMH and normal follicle-stimulating hormone levels. Karyotyping of two peripheral cell lines in girls with TS is recommended to reveal hidden mosaicisms. Ovarian tissue cryopreservation should be offered with caution in a research setting to those with a sufficient ovarian reserve, considering the significant loss of follicles after ovarian tissue cryopreservation and autotransplantation. Physicians should pay attention to the mental health of the girls during the whole process. CLINICAL TRIAL REGISTRATION NUMBER: Trial registration number: NCT03381300- Preservation of Ovarian Cortex Tissue in Girls With Turner Syndrome - Full Text View - ClinicalTrials.gov. Registered on: December 21, 2017. First patient recruited on January 1, 2018.

The lack of evidence behind over-the-counter antioxidant supplements for male fertility patients: a scoping review.

STUDY QUESTION: What is the evidence for over-the-counter antioxidant supplements for male infertility? SUMMARY ANSWER: Less than half of over-the-counter antioxidant supplements for male fertility patients have been tested in a clinical trial, and the available clinical trials are generally of poor quality. WHAT IS KNOWN ALREADY: The prevalence of male infertility is rising and, with this, the market for supplements claiming to improve male fertility is expanding. Up to now, there is limited data on the evidence for these over-the-counter supplements. STUDY DESIGN SIZE DURATION: Amazon, Google Shopping and other relevant shopping websites were searched on 24 June 2022 with the following terms: 'supplements', 'antioxidants', 'vitamins', AND 'male fertility', 'male infertility', 'male subfertility', 'fertility men', 'fertility man'. All supplements with a description of ingredients in English, Dutch, French, Spanish, or German were included. Subsequently, Pubmed and Google Scholar were searched for studies that included the supplements. PARTICIPANTS/MATERIALS SETTING METHODS: Inclusion criteria were supplements with antioxidant properties, of which the main purpose was to improve male fertility. Included supplements must be available without a doctor's prescription. Supplements containing plant extracts were excluded, as well as supplements of which the content or dosage was not clear. The ingredients, dosage, price and health claims of the supplements were recorded. We assessed whether substances in the supplements exceeded the recommended dietary allowance (RDA) or tolerable upper intake level (UL). All clinical trials and animal studies investigating included supplements were selected for this review. Clinical trials were assessed for risk of bias with a risk of bias tool appropriate for the study design. MAIN RESULTS AND THE ROLE OF CHANCE: There were 34 eligible antioxidant supplements found, containing 48 different active substances. The average price per 30 days was 53.10 US dollars. Most of the supplements (27/34, 79%) contained substances in a dosage exceeding the recommended daily allowance (RDA). All manufacturers of the supplements made health claims related to the improvement of sperm quality or male fertility. For 13 of the 34 supplements (38%), published clinical trials were available, and for one supplement, only an animal study was found. The overall quality of the included studies was poor. Only two supplements were tested in a good quality clinical trial. LIMITATIONS REASONS FOR CAUTION: As a consequence of searching shopping websites, a comprehensive search strategy could not be formulated. Most supplements were excluded because they contained plant extracts or because supplement information was not available (in an appropriate language). WIDER IMPLICATIONS OF THE FINDINGS: This is the first review that gives an insight into the market of male fertility supplements as available to infertility patients and other men seeking to improve their fertility. Earlier reviews have focused only on supplements with published clinical trials. However, we show that more than half of the supplements have not been tested in a clinical trial. To our knowledge, this review is the first to assess the dosage of supplements in relation to the RDA. In agreement with the literature, we found that the evidence on male fertility supplements is generally of poor quality. This review should urge pharmaceutical companies to evaluate their products in randomized controlled trials in order to provide people with substantiated information. STUDY FUNDING/COMPETING INTERESTS: The research position of W.R.d.L. is funded by an unrestricted grant from Goodlife Pharma. W.R.d.L., K.F., and J.P.d.B. are in the research team of a clinical trial on Impryl®, one of the supplements included in this review. REGISTRATION NUMBER: N/A.

Exploring X Chromosomal Aberrations in Ovarian Cells by using Fluorescence In Situ Hybridization.

Millions of people worldwide deal with issues concerning fertility. Reduced fertility, or even infertility, may be due to many different causes, including genetic disorders, of which chromosomal abnormalities are the most common. Fluorescence in situ hybridization (FISH) is a well-known and frequently used method to detect chromosomal aberrations in humans. FISH is mainly used for the analysis of chromosomal abnormalities in the spermatozoa of males with numerical or structural chromosomal aberrations. Furthermore, this technique is also frequently applied in females to detect X chromosomal aberrations that are known to cause ovarian dysgenesis. However, information on the X chromosomal content of ovarian cells from females with X chromosomal aberrations in lymphocytes and/or buccal cells is still lacking. The aim of this study is to advance basic research regarding X chromosomal aberrations in females, by presenting two methods based on FISH to identify the X chromosomal content of ovarian cells. First, a method is described to determine the X chromosomal content of isolated ovarian cells (oocytes, granulosa cells, and stromal cells) in non-grafted ovarian cortex tissue from females with X chromosomal aberrations. The second method is directed at evaluating the effect of chromosomal aberrations on folliculogenesis by determining the X chromosomal content of ovarian cells of newly formed secondary and antral follicles in ovarian tissue, from females with X chromosomal aberrations after long-term grafting into immunocompromised mice. Both methods could be helpful in future research to gain insight into the reproductive potential of females with X chromosomal aberrations.

Deciding on future fertility: considerations of girls with Turner syndrome and their parents to opt for or against ovarian tissue cryopreservation.

RESEARCH QUESTION: What are the considerations of girls with Turner syndrome and their parents to opt for or against ovarian tissue cryopreservation (OTC)? DESIGN: Semi-structured in-depth interviews were conducted with girls with Turner syndrome and their parents until data saturation was reached. Participants were recruited through purposive sampling. Data were analysed using a thematic analysis approach. RESULTS: Thirteen parents and five girls who opted for OTC, and seven parents and three girls who declined OTC, were interviewed. Parents and girls mentioned that OTC offered hope, an opportunity to have genetic offspring and clarity about their current fertility status. Most participants were not afraid of the risks of surgery and trusted healthcare providers with this procedure. In contrast, families had to deal with uncertainties, owing to the lack of information on the success rate and long-term consequences of OTC in this group. Families indicated that they had to go through an important decision-making process in a short period of time, because of the limited number of participants in the OTC study. CONCLUSION: A new opportunity and hope for future fertility were considerations for opting for OTC. However, OTC also came with uncertainties owing to the experimental nature of this procedure in girls with Turner syndrome. Healthcare providers could share these experiences with girls with Turner syndrome and their parents to improve fertility-preservation counselling in this group.

Assessment of folliculogenesis in ovarian tissue from young patients with Turner syndrome using a murine xenograft model.

OBJECTIVE: To study the impact of aneuploid granulosa and stromal cells on folliculogenesis of small ovarian follicles from patients with mosaic Turner syndrome (TS) using a murine xenograft model. DESIGN: Laboratory study. SETTING: University hospital. PATIENT(S): Ovarian cortical tissue was obtained by laparoscopic surgery from 18 patients with mosaic TS (aged 5-19 years) and 13 controls (aged 5-18 years). INTERVENTION(S): Part of each tissue fragment was used to karyotype ovarian cells in nongrafted tissue by fluorescence in situ hybridization. The remaining tissue was xenografted to severe combined immunodeficient mice for 5 months. Grafted tissue was analyzed for aneuploidy, and follicle density and morphology were determined. Expressions of proliferating cell nuclear antigen and anti-Müllerian hormone were investigated by immunohistochemistry. MAIN OUTCOME MEASURE(S): The impact of aneuploid granulosa and stromal cells on folliculogenesis. Fluorescence in situ hybridization of ovarian tissue before grafting was performed to determine the level of aneuploidy in stromal cells and oocytes and granulosa of small follicles. After xenografting, the level of aneuploidy of the newly formed layers of granulosa cells was again determined in secondary and antral follicles. RESULT(S): Follicle density in ovarian tissue from patients with TS was significantly lower than in controls before grafting. Fluorescence in situ hybridization analysis confirmed that 101 of 104 oocytes from nongrafted tissue of patients with TS showed normal X chromosome content, whereas granulosa and stromal cells were mainly 45,X. Fragments from 12 patients with TS contained follicles at all stages after xenografting, including secondary and antral follicles. Follicle density in patients with TS and controls decreased significantly after grafting. Moreover, a shift from high to low proportions of 45,X granulosa cells was observed during folliculogenesis. Expression of proliferating cell nuclear antigen in follicles from patients with TS increased significantly during grafting. Secretion of anti-Müllerian hormone was impaired before grafting in peripubertal/postpubertal girls with TS, but recovered after grafting. CONCLUSION(S): Our study showed that small follicles from patients with mosaic TS undergoes folliculogenesis, despite the presence of aneuploid granulosa and stromal cells. Ovarian tissue cryopreservation could therefore be a valid option to preserve fertility in young patients with mosaic TS if sufficient numbers of follicles are present, thus preferably before the age of 12.

Web-based Guidance for Assisted Reproductive Technology With an Online App (myFertiCare): Quantitative Evaluation With the HOT-fit Framework.

BACKGROUND: Assisted reproductive technologies (ARTs) are considered to be physically and mentally stressful. During their treatment trajectory, couples express high information and communication needs. They appreciate using the internet to obtain fertility-related information. In a previous study, we developed myFertiCare, an eHealth tool providing personalized information and interactive functionalities for infertile couples in order to improve patient-centered care. The app has already been successful in qualitative evaluations of usability. OBJECTIVE: The aim of the current study is to quantitatively evaluate the implementation of myFertiCare by using the human, organizational, and technology-fit (HOT-fit) framework and to study the effects of using myFertiCare on couples' knowledge about infertility, their experience of the burden of infertility, and their experience of patient-centered care. With these results, implementation can be further improved, and patient-centered care can be enhanced. METHODS: A quantitative study was performed based on the HOT-fit framework using validated questionnaires focusing on the human, organizational, and technology domains. Questions were added on the effect of using myFertiCare on couples' knowledge about infertility and treatment. Questions regarding the burden of infertility, the burden of infertility treatment, and the experience of patient-centeredness were based on the main items of the validated fertility quality of life (FertiQoL) and Patient-Centredness Questionnaire-Infertility questionnaires, respectively. Also, nonusers of the app were included to explore motivations for not using the app and identify opportunities for improvement. Finally, user data were analyzed to provide insight into multiple variables concerning app use. RESULTS: In the human and technology domains, myFertiCare showed good system usability, high user satisfaction, and high information and interface quality. In the organizational domain, implementation was considered to be sufficient by both patients and staff. Use of the app increased knowledge about the treatment, improved coping with the treatment, and enhanced the experience of patient-centeredness. User data showed that women were the main app users and that use of the app gradually declined during the treatment trajectory. CONCLUSIONS: A multi-faceted online app, myFertiCare, has been successfully evaluated quantitatively for implementation by using the HOT-fit framework. Use of the app increased knowledge about the treatment, improved coping with the treatment, and enhanced the experience of patient-centeredness. App use could be improved by creating more publicity. By providing myFertiCare, professionals in fertility care are supported in guiding patients through their treatment trajectory and in delivering patient-centered care.

Quality of integrated female oncofertility care is suboptimal: A patient-reported measurement.

BACKGROUND: Clinical practice guidelines recommend to inform female cancer patients about their infertility risks due to cancer treatment. Unfortunately, it seems that guideline adherence is suboptimal. In order to improve quality of integrated female oncofertility care, a systematic assessment of current practice is necessary. METHODS: A multicenter cross-sectional survey study in which a set of systematically developed quality indicators was processed, was conducted among female cancer patients (diagnosed in 2016/2017). These indicators represented all domains in oncofertility care; risk communication, referral, counseling, and decision-making. Indicator scores were calculated, and determinants were assessed by multilevel multivariate analyses. RESULTS: One hundred twenty-one out of 344 female cancer patients participated. Eight out of 11 indicators scored below 90% adherence. Of all patients, 72.7% was informed about their infertility, 51.2% was offered a referral, with 18.8% all aspects were discussed in counseling, and 35.5% received written and/or digital information. Patient's age, strength of wish to conceive, time before cancer treatment, and type of healthcare provider significantly influenced the scores of three indicators. CONCLUSIONS: Current quality of female oncofertility care is far from optimal. Therefore, improvement is needed. To achieve this, improvement strategies that are tailored to the identified determinants and to guideline-specific barriers should be developed.

Strategies to safely use cryopreserved ovarian tissue to restore fertility after cancer: a systematic review.

Ovarian tissue cryopreservation and subsequent autotransplantation is a successful technique for fertility preservation in oncological patients. However, there are concerns regarding safety, as the graft may contain malignant cells that could lead to the reintroduction of cancer. To circumvent this problem several experimental strategies are being pursued. This systematic review was conducted to provide an overview of the strategies aiming to safely use cryopreserved human ovarian tissue to restore fertility after cancer. Thirty-one studies were included, covering five different experimental strategies: (i) in-vitro maturation of oocytes, (ii) constructing an artificial ovary as a scaffold for reseeding pre-antral follicles, (iii) purging strategies aimed at the eradication of contaminating malignant cells, (iv) maturation of oocytes by xenotransplantation, and (v) stem cell-based oogenesis. These strategies to circumvent the reintroduction of cancer cells through ovarian tissue autotransplantation are being developed, but so far have not reached the stage of clinical trials. Further research is required to establish their risks and effectiveness while the ethical aspects associated with these strategies also need to be discussed. Despite the fact that these experimental procedures are still under development, they might provide safe fertility restoration options for oncological patients in the future.

Male or female sterilization - the decision making process: Counselling and regret.

OBJECTIVE(S): To analyze the decision-making process of both male and female sterilization in order to improve counselling and prevent regret after sterilization in the future. STUDY DESIGN: An online questionnaire regarding sterilization (counselling, sources of information and regret) was promoted on Facebook, Twitter and LinkedIn. A total of 1107 men and women who had undergone or considered sterilization in the Netherlands filled in the questionnaire. RESULTS: A total of 88.9 % of the sterilized group and 67.4 % in the considered group responded that they felt well informed when they considered sterilization. However, less than half of the participants in both groups knew about all different sterilization methods. In both groups participants reported they consulted their partner the most when they considered sterilization. After sterilization 7.7 % reported having regret. Regret was reported more often when participants were sterilized ≤ 30 years. Most important reasons for regret reported by males were complications, pain, a new wish to conceive and divorce/remarriage. Most important reasons for regret reported by females were pain, complications, a new wish to conceive and menstrual symptoms. A total of 21.1 % in the sterilized and 38.0 % in the considered group responded they would have liked to use a decision aid when they considered sterilization. CONCLUSIONS: Findings of this study provide insight in the decision-making process regarding sterilization. There is a lack of knowledge of different methods of sterilization and 7.7% regrets their sterilization afterwards. Furthermore, the results show an importance of developing a decision aid for couples considering sterilization.

Exploration of fertility and early menopause related information needs and development of online information for young breast cancer survivors.

BACKGROUND: Approximately half of premenopausal women diagnosed with breast cancer desire to conceive after they finish treatment. Counseling about the risk of infertility prior to cancer treatment has been proven to improve quality of life after cancer treatment. As a result of this, guidelines focus on informing women on this topic prior to treatment. However, it is equally important to provide fertility related information after primary treatment has been completed, when the wish to conceive might become actual. Therefore, the aim of this study was to identify the fertility and early menopause related information needs of young breast cancer survivors and to design, develop and implement online information material with input of stakeholders. METHODS: A phenomenological qualitative study consisting of four phases was performed: identification of information needs through semi-structured interviews from a professional perspective (1) and a patient perspective (2). Exploration of stakeholders perspective regarding development and implementation of online information material (3) and development and implementation of the information material (4). RESULTS: Professionals indicated that there are no guidelines regarding the provision of fertility related information during cancer survivorship. Survivors reported unmet information needs. Women identified the following as most important information needs (a) fertility preservation options, (b) the risk of menopause or infertility, and (c) long term consequences of early menopause. A wide range of stakeholders involved in breast cancer care were interviewed. Based on their proposed design the information material was implemented on a nationwide website aiming at informing and supporting breast cancer patients. CONCLUSIONS: Fertility and early menopause related information needs of young breast cancer survivors and their professionals were identified. Information material has been designed, developed and nationally implemented. This way, professionals in breast cancer care are provided with an information tool that helps them meet the information needs and preferences of their patients.

The Decision-Making Process regarding Ovarian Tissue Cryopreservation in Girls with Turner Syndrome by Patients, Parents, and Healthcare Providers: A Mixed-Methods Study.

INTRODUCTION: Ovarian tissue cryopreservation (OTC) has proven to be effective in other patient groups, but the effectiveness in girls with Turner syndrome (TS) is still unclear. Guidelines for counselling about OTC in TS are lacking. The aim of this study was to gain insight into the experiences of patients, parents, and healthcare providers with the decision-making process regarding OTC in girls with TS. METHODS: Within a year after counselling, a survey was sent to 132 girls with TS and their parents. Furthermore, focus groups were conducted with (1) gynaecologists with subspeciality reproductive medicine, (2) paediatric endocrinologists, (3) parents of girls aged 2-12, and (4) parents of girls aged 13-18. Transcripts were analysed using a thematic analysis approach. RESULTS: The response rate of the survey was 45%. Of the survey respondents, 90% appreciated counselling regarding their future parenting options and considered it an addition to existing healthcare. Girls with TS and their parents indicated that the option of OTC raised hope for future genetic offspring and instantly made them feel that their only option was to seize this opportunity. Gynaecologists and paediatricians found it challenging to truly make families grasp a realistic perspective of OTC in girls with TS. DISCUSSION AND CONCLUSION: Offering young girls with TS the possibility of fertility preservation in an experimental setting raised high hopes and led to challenges for healthcare providers in ensuring a considered decision. The appropriate moment for counselling should be tailored to the individual and discussed with patient, parents, and paediatrician.

The Tell me tool: The development and feasibility of a tool for person-centred infertility care.

BACKGROUND: An important-and often missing-element of person-centred care is the inclusion of individual patients' values and preferences. This is challenging but especially important for high-burden fertility treatments. We describe the development of a clinical tool that aims to facilitate the delivery of person-centred fertility care by giving insight into the patients' values and preferences. METHODS: We developed the Tell me tool following the three principles of user-centred design: (1) early and continual focus on users; (2) iterative design; (3) measurement of user behaviour. Accordingly, our methods consisted of three phases: (1) conducting semi-structured interviews with 18 couples undergoing fertility treatment, followed by a consensus meeting with relevant stakeholders; (2) performing seven iterative improvement rounds; (3) testing the feasibility of the tool in 10 couples. RESULTS: The Tell me tool consists of a ranking assignment of 13 themes and two open-ended questions. These themes relate to the couples' wellbeing and experience of the treatment, such as mental health and shared decision making. The open-ended questions ask them to write down what matters most to them. The field test showed variation between the individual patients' answers. The tool proved to highlight what is important to the individual patient and gives insight into patients' personal contexts. CONCLUSIONS: We developed a tool that gives insight into the values and preferences of the individual patient. The tool seems feasible for facilitating person-centred fertility care. PATIENT OR PUBLIC CONTRIBUTION: The tool was developed with a user-centred design that strongly involved patients.