The feasibility of an anti-inflammatory diet in endometriosis: barriers and facilitators perceived by endometriosis patients.

RESEARCH QUESTION: What is the feasibility of an anti-inflammatory diet in women diagnosed with endometriosis? DESIGN: Qualitative study using semi-structured focus groups and individual interviews among patients with endometriosis. Transcripts of the focus groups and interviews were thematically analysed using ATLAS.ti 9. To identify and structure the ideas and views from the focus groups and interviews, two behavioural change models were used. The Capability Opportunity Motivation Behaviour (COM-B) model and domains of the Theoretical Domains Framework (TDF) helped to identify factors that make adherence to an anti-inflammatory diet more or less feasible for women with endometriosis. RESULTS: The study population consisted of 23 patients with endometriosis. Numerous perceived barriers and facilitators were identified from all COM-B components and 13 out of 15 TDF domains. Knowledge and social influences were the most prominent TDF domains. Key barriers were eating with others; disbelief in a patients' own capability regarding specific dietary guidelines; concerns about taste; lack of knowledge on how to follow the diet; lack of noticeable beneficial effect; and lack of intention to follow the diet to full extent. Key facilitators were receiving social support; general confidence in a participant's own capabilities; knowing how and why to follow the diet; noticing beneficial effect; and belief that the diet would alleviate symptoms. CONCLUSION: Provision of knowledge, stimulating social support and enhancing self-efficacy should be emphasized. Overall, an anti-inflammatory diet in endometriosis patients, especially when identified barriers and facilitators are addressed in an intervention, is feasible.

The Promises of Natural Killer Cell Therapy in Endometriosis.

Endometriosis is a gynaecological disease defined by the growth of endometrium-like tissue outside the uterus. The disease is present in approximately 5-10% of women of reproductive age and causes pelvic pain and infertility. The pathophysiology is not completely understood, but retrograde menstruation and deficiency in natural killer (NK) cells that clear endometriotic cells in the peritoneal cavity play an important role. Nowadays, hormonal therapy and surgery to remove endometriosis lesions are used as treatment. However, these therapies do not work for all patients, and hormonal therapy prevents patients from getting pregnant. Therefore, new treatment strategies should be developed. Since the cytotoxicity of NK cells is decreased in endometriosis, we performed a literature search into the possibility of NK cell therapy. Available treatment options include the inhibition of receptor-ligand interaction for KIR2DL1, NKG2A, LILRB1/2, and PD-1/PD-L1; inhibition of TGF-ß; stimulation of NK cells with IL-2; and mycobacterial treatment with BCG. In preclinical work, these therapies show promising results but unfortunately have side effects, which have not specifically been studied in endometriosis patients. Before NK cell treatment can be used in the clinic, more research is needed.

Diet quality and perceived effects of dietary changes in Dutch endometriosis patients: an observational study.

RESEARCH QUESTION: What is the current diet of women with endometriosis, in terms of adherence to dietary guidelines and use of diets, and what are the perceived effects of dietary modifications? DESIGN: In this online explorative observational study, the Dutch Healthy Diet 2015 index (DHD-15) and quality of life (QoL) with the Endometriosis Health Profile-30 questionnaire (EHP-30) were used to assess diet quality. RESULTS: The questionnaires were completed by 157 participants. Many participants made one or more dietary adaptations for their endometriosis, in the form of a specific diet (46.5%), with the use of dietary supplements (56.1%), with other dietary adjustments (64.3%), or all. Endometriosis patients had a significantly lower DHD-15 score, indicating a lower diet quality than a healthy reference group (P = 0.004). In the endometriosis group, diet users had a significantly higher total DHD-15 score than non-diet users (P < 0.0001). Diet quality was not correlated with QoL (Pearson's r = -0.010, P = 0.904). Many specific dietary adjustments (71.3%), however, were reported to reduce endometriosis pain-related symptoms. The removal of gluten, dairy or soy, as well as the addition of vegetables, showed the greatest perceived reductions of symptoms in participants. CONCLUSIONS: Although no specific dietary adjustment was found to increase QoL, endometriosis patients do feel that dietary adjustments have a beneficial effect on their symptoms. Therefore, more research is needed to gain evidence about the specific effects of nutrients on endometriosis symptoms.

Patients' perspective on cognitive behavioural therapy after surgical treatment of endometriosis: a qualitative study.

RESEARCH QUESTION: Would adding cognitive behavioural therapy (CBT) to the treatment of endometriosis improve the quality of life of patients suffering from endometriosis-associated pain? The aim of this study was to identify if patients believed CBT should be added to endometriosis treatment and which form of CBT they would prefer: face-to-face individual or group, or web-based individual, sessions. DESIGN: Between November 2019 and January 2020, semi-structured focus groups were conducted using an interview guide to ensure all topics were discussed. Data collection was continued until saturation was obtained. The focus groups were transcribed word for word and openly encoded. Finally, themes were formulated. RESULTS: All participating women believed CBT should be offered to patients undergoing endometriosis surgery. They believed it could be an asset to improve quality of life. Participants preferred either in-person individual or group therapy. They stressed the importance of being offered a custom-made treatment plan, individually tailored to the different needs of different patients. CONCLUSION: This study has shown that patients with endometriosis believe that CBT should be added to the standard treatment regimen of endometriosis in either group or individual face-to-face sessions, because they expect that CBT will improve their quality of life after surgery.

The impact of the COVID-19 pandemic on infertility patients and endometriosis patients in the Netherlands.

RESEARCH QUESTION: How do infertility patients, endometriosis patients and health-care providers rate virtual care as an alternative to physical consultations during the first lockdown of the coronavirus disease 2019 (COVID-19) pandemic in the Netherlands, and how does this influence quality of life and quality of care? DESIGN: Infertility patients and endometriosis patients from a university hospital and members of national patient organizations, as well as healthcare providers in infertility and endometriosis care, were asked to participate between May and October 2020. The distributed online questionnaires consisted of an appraisal of virtual care and an assessment of fertility-related quality of life (FertiQol) and patient-centredness of endometriosis care (ENDOCARE). RESULTS: Questionnaires were returned by 330 infertility patients, 181 endometriosis patients and 101 healthcare providers. Of these, 75.9% of infertility patients, 64.8% of endometriosis patients and 80% of healthcare providers rated telephone consultations as a good alternative to physical consultations during the COVID-19-pandemic. Only 21.3%, 14.8% and 19.2% of the three groups rated telephone consultations as a good replacement for physical consultations in the future. A total of 76.6% and 35.9% of the infertility and endometriosis patients reported increased levels of stress during the pandemic. Infertility patients scored lower on the FertiQol, while the ENDOCARE results care seem comparable to the reference population. CONCLUSIONS: Virtual care seems to be a good alternative for infertility and endometriosis patients in circumstances where physical consultations are not possible. Self-reported stress is especially high in infertility patients during the COVID-19-pandemic. Healthcare providers should aim to improve their patients' ability to cope.

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

RESEARCH QUESTION: What are the long-term costs and effects of oil- versus water-based contrast in infertile women undergoing hysterosalpingography (HSG)? DESIGN: This economic evaluation of a long-term follow-up of a multicentre randomized controlled trial involved 1119 infertile women randomized to HSG with oil- (n = 557) or water-based contrast (n = 562) in the Netherlands. RESULTS: In the oil-based contrast group, 39.8% of women needed no other treatment, 34.6% underwent intrauterine insemination (IUI) and 25.6% had IVF/intracytoplasmic sperm injection (ICSI) in the 5 years following HSG. In the water-based contrast group, 35.0% of women had no other treatment, 34.2% had IUI and 30.8% had IVF/ICSI in the 5 years following HSG (P = 0.113). After 5 years of follow-up, HSG using oil-based contrast resulted in equivalent costs (mean cost difference -€144; 95% confidence interval [CI] -€579 to +€290; P = 0.515) for a 5% increase in the cumulative ongoing pregnancy rate compared with HSG using water-based contrast (80% compared with 75%, Relative Risk (RR) 1.07; 95% CI 1.00-1.14). Similarly, HSG with oil-based contrast resulted in equivalent costs (mean cost difference -€50; 95% CI -€576 to +€475; P = 0.850) for a 7.5% increase in the cumulative live birth rate compared with HSG with water-based contrast (74.8% compared with 67.3%, RR 1.11; 95% CI 1.03-1.20), making it the dominant strategy. Scenario analyses suggest that the oil-based contrast medium is the dominant strategy up to a price difference of €300. CONCLUSION: Over a 5-year follow-up, HSG with an oil-based contrast was associated with a 5% increase in ongoing pregnancy rate, a 7.5% increase in live birth rate and similar costs to HSG with water-based contrast.

Oil-Based or Water-Based Contrast for Hysterosalpingography in Infertile Women.

BACKGROUND: Pregnancy rates among infertile women have been reported to increase after hysterosalpingography, but it is unclear whether the type of contrast medium used (oil-based or water-soluble contrast) influences this potential therapeutic effect. METHODS: We performed a multicenter, randomized trial in 27 hospitals in the Netherlands in which infertile women who were undergoing hysterosalpingography were randomly assigned to undergo this procedure with the use of oil-based or water-based contrast. Subsequently, couples received expectant management or the women underwent intrauterine insemination. The primary outcome was ongoing pregnancy within 6 months after randomization. Outcomes were analyzed according to the intention-to-treat principle. RESULTS: A total of 1119 women were randomly assigned to hysterosalpingography with oil contrast (557 women) or water contrast (562 women). A total of 220 of 554 women in the oil group (39.7%) and 161 of 554 women in the water group (29.1%) had an ongoing pregnancy (rate ratio, 1.37; 95% confidence interval [CI], 1.16 to 1.61; P<0.001), and 214 of 552 women in the oil group (38.8%) and 155 of 552 women in the water group (28.1%) had live births (rate ratio, 1.38; 95% CI, 1.17 to 1.64; P<0.001). Rates of adverse events were low and similar in the two groups. CONCLUSIONS: Rates of ongoing pregnancy and live births were higher among women who underwent hysterosalpingography with oil contrast than among women who underwent this procedure with water contrast. (Netherlands Trial Register number, NTR3270 .).

Barriers and facilitators to the timely diagnosis of endometriosis in primary care in the Netherlands.

BACKGROUND: Endometriosis is an invalidating gynaecological condition in women of reproductive age, and a frequent cause of infertility. Unfortunately, the condition is characterized by a long interval between onset of symptoms and diagnosis. GPs in the Netherlands are educated to provide basic gynaecological care and serve as gatekeepers for specialist medical care. Therefore, it is of great importance that they recognize signs and symptoms possibly caused by endometriosis to initiate adequate actions. OBJECTIVE: The main objective of this study was to identify barriers and facilitators to the timely diagnosis of endometriosis from the GPs' perspective. METHODS: Semi-structured focus group discussions with GPs were organized throughout the Netherlands. The participants were encouraged to brainstorm about their perspective on daily practice regarding endometriosis and suggestions for interventions to enable early diagnosis and treatment. Analysis was based on grounded theory methodology. RESULTS: Forty-three GPs participated in six focus groups. Analysis of the transcripts revealed relevant determinants of practice in four main themes: professionals' experience and competence, patient characteristics, guideline factors and professional collaboration. A lack of knowledge and awareness appeared to result in a low priority for establishing the diagnosis of endometriosis, especially in young women. Infertility, patient engagement and a recent serious case or training facilitated referral. CONCLUSION: Several factors in daily primary health care contribute to the diagnostic delay in endometriosis. Future interventions to reduce this delay may be aimed at increasing awareness by means of education, incorporating the subject into national clinical guidelines and improvements in interdisciplinary collaboration.

Randomized Trial of a Lifestyle Program in Obese Infertile Women.

BACKGROUND: Small lifestyle-intervention studies suggest that modest weight loss increases the chance of conception and may improve perinatal outcomes, but large randomized, controlled trials are lacking. METHODS: We randomly assigned infertile women with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 29 or higher to a 6-month lifestyle intervention preceding treatment for infertility or to prompt treatment for infertility. The primary outcome was the vaginal birth of a healthy singleton at term within 24 months after randomization. RESULTS: We assigned women who did not conceive naturally to one of two treatment strategies: 290 women were assigned to a 6-month lifestyle-intervention program preceding 18 months of infertility treatment (intervention group) and 287 were assigned to prompt infertility treatment for 24 months (control group). A total of 3 women withdrew consent, so 289 women in the intervention group and 285 women in the control group were included in the analysis. The discontinuation rate in the intervention group was 21.8%. In intention-to-treat analyses, the mean weight loss was 4.4 kg in the intervention group and 1.1 kg in the control group (P<0.001). The primary outcome occurred in 27.1% of the women in the intervention group and 35.2% of those in the control group (rate ratio in the intervention group, 0.77; 95% confidence interval, 0.60 to 0.99). CONCLUSIONS: In obese infertile women, a lifestyle intervention preceding infertility treatment, as compared with prompt infertility treatment, did not result in higher rates of a vaginal birth of a healthy singleton at term within 24 months after randomization. (Funded by the Netherlands Organization for Health Research and Development; Netherlands Trial Register number, NTR1530.).

The impact of menstrual symptoms on everyday life: a survey among 42,879 women.

BACKGROUND: Menstrual symptoms such as dysmenorrhea, heavy menstrual bleeding, and perimenstrual mood disorders are known to be widespread among the general population. From studies in patients with endometriosis and premenstrual disorder, it has been shown that these symptoms can have a large impact on women's quality of life and account for substantial health care use. Furthermore, it is estimated that many women initially do not consult a doctor while facing menstrual symptoms. Consequently, the impact of menstrual symptoms on daily activities in the general population is unknown. OBJECTIVE: To obtain a nationwide overview of menstrual symptoms and their impact on everyday activities. STUDY DESIGN: Nationwide, cross-sectional, internet-based survey among 42,879 women aged 15-45 years, conducted from July to October 2017. OUTCOME MEASURES: presence of menstrual symptoms, pain or intensity score, impact on daily activities. RESULTS: Dysmenorrhea was the most common symptom, with a prevalence of 85%, followed by psychological complaints (77%), and tiredness (71%). During their menstrual period, 38% of all women reported not to be able to perform all their regular daily activities. From the women that had to skip tasks because of their symptoms, only 48.6% told their family that menstrual symptoms were the reason for the transfer of tasks. CONCLUSION: Menstrual symptoms are widespread among the general population. One in 3 women quit daily activities owing to menstrual symptoms. Half of all women did not mention menstrual complaints being the reason for transferring tasks in a family setting. These results must be interpreted with caution owing to the potential for selection bias. However, considering the impact of menstrual symptoms on daily activities in a large group of women, it is time to open the societal dialogue and improve education for both patients and doctors.

Health state utilities for infertility and subfertility.

BACKGROUND: Health state utility values allow for comparison of treatments across different diseases. Utility values for fertility-impaired health states are currently unavailable. Such values are necessary in order to determine the relative costs-effectiveness of fertility treatments. METHODS: This study aimed to determine utility weights for infertile and subfertile health states. In addition, it explored the Dutch general population's opinions regarding the inclusion of infertility treatments in the Dutch health insurers' basic benefit package. An online questionnaire was designed to determine the health-related quality of life values of six fertility-impaired health states. The study population consisted of a representative sample of the Dutch adult population. Respondents were asked to evaluate the health states through direct health valuation methods, i.e. the Visual Analogue Scale (VAS) and the Time Trade-Off (TTO) method. In addition, respondents were asked about their opinions regarding reimbursement of fertility-related treatments. RESULTS: The respondents' (n = 767) VAS scores ranged from 0.640 to 0.796. TTO utility values ranged from 0.792 to 0.868. Primary infertility and subfertility was valued lower than secondary infertility and subfertility. In total, 92% of the respondents stated that fertility treatments should be fully or partially reimbursed by the health insurance basic benefit package. CONCLUSIONS: Having fertility problems results in substantial disutilities according to the viewpoint of the Dutch general population. The results make it possible to compare the value for money of infertility treatment to that of treatments in other disease areas. There is strong support among the general population for reimbursing fertility treatments through the Dutch basic benefit package.

Hysteroscopy before in-vitro fertilisation (inSIGHT): a multicentre, randomised controlled trial.

BACKGROUND: Hysteroscopy is often done in infertile women starting in-vitro fertilisation (IVF) to improve their chance of having a baby. However, no data are available from randomised controlled trials to support this practice. We aimed to assess whether routine hysteroscopy before the first IVF treatment cycle increases the rate of livebirths. METHODS: We did a pragmatic, multicentre, randomised controlled trial in seven university hospitals and 15 large general hospitals in the Netherlands. Women with a normal transvaginal ultrasound of the uterine cavity and no previous hysteroscopy who were scheduled for their first IVF treatment were randomly assigned (1:1) to either hysteroscopy with treatment of detected intracavitary abnormalities before starting IVF (hysteroscopy group) or immediate start of the IVF treatment (immediate IVF group). Randomisation was done with web-based concealed allocation and was stratified by centre with variable block sizes. Participants, doctors, and outcome assessors were not masked to the assigned group. The primary outcome was ongoing pregnancy (detection of a fetal heartbeat at >12 weeks of gestation) within 18 months of randomisation and resulting in livebirth. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01242852. FINDINGS: Between May 25, 2011, and Aug 27, 2013, we randomly assigned 750 women to receive either hysteroscopy (n=373) or immediate IVF (n=377). 209 (57%) of 369 women eligible for assessment in the hysteroscopy group and 200 (54%) of 373 in the immediate IVF group had a livebirth from a pregnancy during the trial period (relative risk 1·06, 95% CI 0·93-1·20; p=0·41). One (<1%) woman in the hysteroscopy group developed endometritis after hysteroscopy. INTERPRETATION: Routine hysteroscopy does not improve livebirth rates in infertile women with a normal transvaginal ultrasound of the uterine cavity scheduled for a first IVF treatment. Women with a normal transvaginal ultrasound should not be offered routine hysteroscopy. FUNDING: The Dutch Organisation for Health Research and Development (ZonMW).

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

STUDY QUESTION: Does an increased FSH dose result in higher cumulative live birth rates in women with a predicted poor ovarian response, apparent from a low antral follicle count (AFC), scheduled for IVF or ICSI? SUMMARY ANSWER: In women with a predicted poor ovarian response (AFC < 11) undergoing IVF/ICSI, an increased FSH dose (225/450 IU/day) does not improve cumulative live birth rates as compared to a standard dose (150 IU/day). WHAT IS KNOWN ALREADY: In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can predict ovarian response to stimulation. The FSH starting dose is often adjusted based on the ORT from the belief that it will improve live birth rates. However, the existing RCTs on this topic, most of which show no benefit, are underpowered. STUDY DESIGN, SIZE, DURATION: Between May 2011 and May 2014, we performed an open-label multicentre RCT in women with an AFC < 11 (Dutch Trial Register NTR2657). The primary outcome was ongoing pregnancy achieved within 18 months after randomization and resulting in a live birth. We needed 300 women to assess whether an increased dose strategy would increase the cumulative live birth rate from 25 to 40% (two-sided alpha-error 0.05, power 80%). PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with an AFC ≤ 7 were randomized to an FSH dose of 450 IU/day or 150 IU/day, and women with an AFC 8-10 were randomized to 225 IU or 150 IU/day. In the standard group, dose adjustment was allowed in subsequent cycles based on pre-specified criteria. Both effectiveness and cost-effectiveness of the strategies were evaluated from an intention-to-treat perspective. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 511 women were randomized, 234 with an AFC ≤ 7 and 277 with an AFC 8-10. The cumulative live birth rate for increased versus standard dosing was 42.4% (106/250) versus 44.8% (117/261), respectively [relative risk (RR): 0.95 (95%CI, 0.78-1.15), P = 0.58]. As an increased dose strategy was more expensive [delta costs/woman: €1099 (95%CI, 562-1591)], standard FSH dosing was the dominant strategy in our economic analysis. LIMITATIONS, REASONS FOR CAUTION: Despite our training programme, the AFC might have suffered from inter-observer variation. As this open study permitted small dose adjustments between cycles, potential selective cancelling of cycles in women treated with 150 IU could have influenced the cumulative results. However, since first cycle live birth rates point in the same direction we consider it unlikely that the open design masked a potential benefit for the individualized strategy. WIDER IMPLICATIONS OF THE FINDINGS: Since an increased dose in women scheduled for IVF/ICSI with a predicted poor response (AFC < 11) does not improve live birth rates and is more expensive, we recommend using a standard dose of 150 IU/day in these women. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by The Netherlands Organisation for Health Research and Development (ZonMW number 171102020). T.C.T., H.L.T. and S.C.O. received an unrestricted personal grant from Merck BV. H.R.V. receives monetary compensation as a member on an external advisory board for Ferring pharmaceutical BV. B.W.J.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for OvsEva, Merck and Guerbet. F.J.M.B. receives monetary compensation as a member of the external advisory board for Ferring pharmaceutics BV (the Netherlands) and Merck Serono (the Netherlands) for consultancy work for Gedeon Richter (Belgium) and Roche Diagnostics on automated AMH assay development (Switzerland) and for a research cooperation with Ansh Labs (USA). All other authors have nothing to declare. TRIAL REGISTRATION NUMBER: Registered at the ICMJE-recognized Dutch Trial Registry (www.trialregister.nl). Registration number NTR2657. TRIAL REGISTRATION DATE: 20 December 2010. DATE OF FIRST PATIENT'S ENROLMENT: 12 May 2011.

Knowledge of, and treatment strategies for, endometriosis among general practitioners.

Endometriosis is the most common benign gynaecological disorder. The general practitioner (GP) plays an important role in identifying women at early stages of the disease. This study was conducted to acquire information about awareness and knowledge of endometriosis among Dutch GPs, and clinical strategies taken. A total of 101 GPs completed a questionnaire either by email or at a local education meeting. The GPs annually encounter 2.8 women they suspect of having endometriosis. The estimated time to diagnosis was 65.7 months (39.1 months patient delay and 26.6 months doctors delay); 56.7% of GPs primarily refer to a gynaecologist for consultation or diagnostic tests. The GPs answered on average 16.6 out of 28 knowledge questions correctly. Seventy-six out of 87 GPs stated that they needed further education. The results of this study indicate that if a GP considers endometriosis as a diagnosis, adequate action is undertaken. As only limited numbers of women with endometriosis are encountered in their practice, GPs do not recognize immediately the symptoms that may be caused by endometriosis, leading to diagnostic delay. Our findings may help to set up teaching programmes and awareness strategies for first-line medical professionals to enhance timely diagnosis and treatment of endometriosis.

Characteristics, expectations and needs of the dutch endometriosis society members.

UNLABELLED: BACKGROUND/AIM STUDY QUESTION: Endometriosis is associated with a significant reduction in the quality of life and higher depression and anxiety rates. The Dutch Endometriosis Society (ES) was founded to increase the recognition and knowledge in patients and health care professionals, stimulate research and improve care. This study was conducted to explore the characteristics of the members and evaluate their needs and expectations. METHODS: A descriptive questionnaire-based survey was conducted among all members of the ES. The response rate was 51% (n = 571). RESULTS: ES members appear to be highly educated women with a wide variety of endometriosis-related symptoms resulting in considerable restrictions in daily life. Information transmission was considered the main aim of ES (97%), whereas 56% expected social support, and 38% expected advocacy. The majority (71%) reported an improvement in their quality of life after contact with the ES. CONCLUSION: The results of this study underline patients' primary quest for information about endometriosis. Patient support groups such as ES can fulfil a useful role in disseminating knowledge from medical professionals to those suffering a chronic illness, resulting in a greater understanding and ultimately increasing their quality of life.

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 reduction of diagnostic delay in endometriosis.

The (cost-) effectiveness Of Surgical excision of Colorectal endometriosis compared to ART treatment trAjectory (TOSCA study) - a study protocol.

Currently, the optimal treatment to increase the chance of pregnancy and live birth in patients with colorectal endometriosis and subfertility is unknown. Evidence suggests that that both surgery and in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) are effective in improving live birth rate (LBR) among these women. However, the available evidence is of low quality, reports highly heterogeneous results, lacks direct comparison between both treatment options and does not assess whether a combination strategy results in a higher LBR compared to IVF/ICSI-only treatment. Additionally, the optimal timing of surgery within the treatment trajectory remains unclear. The primary objective of the TOSCA study is to assess the effectiveness of surgical treatment (potentially combined with IVF/ICSI) compared to IVF/ICSI-only treatment to increase the chance of an ongoing pregnancy resulting in a live birth in patients with colorectal endometriosis and subfertility, measured by cumulative LBR. Secondary objectives are to assess and compare quality of life and cost-effectiveness in both groups. Patients will be followed for 40 months after inclusion or until live birth. The TOSCA study is expected to be completed in 6 years.

A taxonomy of possible reasons for and against sperm donation.

OBJECTIVE: Various reasons may guide the decision of men to become a sperm donor. Our aim was to identify a comprehensive set of possible reasons for and against sperm donation. DESIGN: Concept mapping. SETTING: Assisted reproduction clinics. SAMPLE: Nine sperm donors and seven non-sperm donors. METHODS: Interviews to obtain statements for and against sperm donation, card-sorting tasks to categorize these statements according to similarity, and hierarchical cluster analysis to structure these categorizations. MAIN OUTCOME MEASURES: Hierarchical structure with reasons for and against sperm donation. RESULTS: The hierarchical structure with 91 reasons comprised selfishness (including narcissism and procreation), psychosocial drives (including altruism, detached procreation, and sexual/financial satisfaction), and psychosocial barriers (including normative and moral barriers related to oneself, one's spouse, the donor child, and society). CONCLUSIONS: The identified hierarchical overview of reasons for and against sperm donation may help potential sperm donors when considering becoming a sperm donor, enable more systematic counseling of potential sperm donors, and guide further research on reasons for and against sperm donation.

Risk Factors for Adhesion-Related Readmission and Abdominal Reoperation after Gynecological Surgery: A Nationwide Cohort Study.

More than half of women in developed countries undergo surgery during their lifetime, putting them at risk of adhesion-related complications. Adhesion-related complications include small bowel obstruction, chronic (pelvic) pain, subfertility, and complications associated with adhesiolysis during reoperation. The aim of this study is to predict the risk for adhesion-related readmission and reoperation after gynecological surgery. A Scottish nationwide retrospective cohort study was conducted including all women undergoing a gynecological procedure as their initial abdominal or pelvic operation between 1 June 2009 and 30 June 2011, with a five-year follow-up. Prediction models for two- and five-year risk of adhesion-related readmission and reoperation were constructed and visualized using nomograms. To evaluate the reliability of the created prediction model, internal cross-validation was performed using bootstrap methods. During the study period, 18,452 women were operated on, and 2719 (14.7%) of them were readmitted for reasons possibly related to adhesions. A total of 2679 (14.5%) women underwent reoperation. Risk factors for adhesion-related readmission were younger age, malignancy as indication, intra-abdominal infection, previous radiotherapy, application of a mesh, and concomitant inflammatory bowel disease. Transvaginal surgery was associated with a lower risk of adhesion-related complications as compared to laparoscopic or open surgeries. The prediction model for both readmissions and reoperations had moderate predictive reliability (c-statistics 0.711 and 0.651). This study identified risk factors for adhesion-related morbidity. The constructed prediction models can guide the targeted use of adhesion prevention methods and preoperative patient information in decision-making.

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

BACKGROUND: Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH). FSH is usually administered in a standard dose. However, due to differences in ovarian reserve between women, ovarian response also differs with potential negative consequences on pregnancy rates. A Markov decision-analytic model showed that FSH dose individualisation according to ovarian reserve is likely to be cost-effective in women who are eligible for IVF. However, this has never been confirmed in a large randomised controlled trial (RCT). The aim of the present study is to assess whether an individualised FSH dose regime based on an ovarian reserve test (ORT) is more cost-effective than a standard dose regime. METHODS/DESIGN: Multicentre RCT in subfertile women indicated for a first IVF or intracytoplasmic sperm injection cycle, who are aged < 44 years, have a regular menstrual cycle and no major abnormalities at transvaginal sonography. Women with polycystic ovary syndrome, endocrine or metabolic abnormalities and women undergoing IVF with oocyte donation, will not be included. Ovarian reserve will be assessed by measuring the antral follicle count. Women with a predicted poor response or hyperresponse will be randomised for a standard versus an individualised FSH regime (150 IU/day, 225-450 IU/day and 100 IU/day, respectively). Participants will undergo a maximum of three stimulation cycles during maximally 18 months. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months after randomisation. Secondary outcomes are parameters for ovarian response, multiple pregnancies, number of cycles needed per live birth, total IU of FSH per stimulation cycle, and costs. All data will be analysed according to the intention-to-treat principle. Cost-effectiveness analysis will be performed to assess whether the health and associated economic benefits of individualised treatment of subfertile women outweigh the additional costs of an ORT. DISCUSSION: The results of this study will be integrated into a decision model that compares cost-effectiveness of the three dose-adjustment strategies to a standard dose strategy. The study outcomes will provide scientific foundation for national and international guidelines. TRIAL REGISTRATION: NTR2657.