The effectiveness of immediate versus delayed tubal flushing with oil-based contrast in women with unexplained infertility (H2Oil-timing study): study protocol of a randomized controlled trial.

BACKGROUND: In women with unexplained infertility, tubal flushing with oil-based contrast during hysterosalpingography leads to significantly more live births as compared to tubal flushing with water-based contrast during hysterosalpingography. However, it is unknown whether incorporating tubal flushing with oil-based contrast in the initial fertility work-up results to a reduced time to conception leading to live birth when compared to delayed tubal flushing that is performed six months after the initial fertility work-up. We also aim to evaluate the effectiveness of tubal flushing with oil-based contrast during hysterosalpingography versus no tubal flushing in the first six months of the study. METHODS: This study will be an investigator-initiated, open-label, international, multicenter, randomized controlled trial with a planned economic analysis alongside the study. Infertile women between 18 and 39 years of age, who have an ovulatory cycle, who are at low risk for tubal pathology and have been advised expectant management for at least six months (based on the Hunault prediction score) will be included in this study. Eligible women will be randomly allocated (1:1) to immediate tubal flushing (intervention) versus delayed tubal flushing (control group) by using web-based block randomization stratified per study center. The primary outcome is time to conception leading to live birth with conception within twelve months after randomization. We assess the cumulative conception rate at six and twelve months as two co-primary outcomes. Secondary outcomes include ongoing pregnancy rate, live birth rate, miscarriage rate, ectopic pregnancy rate, number of complications, procedural pain score and cost-effectiveness. To demonstrate or refute a shorter time to pregnancy of three months with a power of 90%, a sample size of 554 women is calculated. DISCUSSION: The H2Oil-timing study will provide insight into whether tubal flushing with oil-based contrast during hysterosalpingography should be incorporated in the initial fertility work-up in women with unexplained infertility as a therapeutic procedure. If this multicenter RCT shows that tubal flushing with oil-based contrast incorporated in the initial fertility work-up reduces time to conception and is a cost-effective strategy, the results may lead to adjustments of (inter)national guidelines and change clinical practice. TRIAL REGISTRATION NUMBER: The study was retrospectively registered in International Clinical Trials Registry Platform (Main ID: EUCTR2018-004153-24-NL).

Oil-based versus water-based contrast media for hysterosalpingography in infertile women of advanced age, with ovulation disorders or a high risk for tubal pathology: study protocol of a randomized controlled trial (H2Oil2 study).

BACKGROUND: In women with unexplained infertility, tubal flushing with oil-based contrast during hysterosalpingography (HSG) increases ongoing pregnancy and subsequent live birth rates when compared to tubal flushing with water-based contrast. It is currently unclear whether an HSG with oil-based contrast also results in more ongoing pregnancies and live births in women of advanced age, women with ovulation disorders, and women with potential tubal pathology when compared to an HSG with water-based contrast. METHODS: We plan an international, multicentre, open-label, randomized controlled trial (RCT) studying three groups of infertile women who have an indication for tubal patency testing according to their treating physician and additionally; (1) are 39 years of age or older, (2) have an ovulation disorder or (3) have a high risk for tubal pathology based on their medical history. Women with an allergy for iodinated contrast medium are excluded, as are women with diabetes, hyperprolactinemia or untreated hyper- or hypothyroidism, and women with a partner with severe male infertility. After informed consent, women will be randomly allocated to the intervention, tubal flushing with the use of oil-based contrast during HSG or the control group, tubal flushing with the use of water-based contrast during HSG in a 1:1 ratio by the web-based system Castor. The primary endpoint will be ongoing pregnancy leading to live birth with conception within six months after randomization. Secondary outcomes are other pregnancy outcomes, used fertility treatments, adverse events and cost-effectiveness. Based on the expected ongoing pregnancy rate of 17% in the control group and 27% in the intervention group, the sample size will be 930 women (465 per group). Study inclusion is expected to be complete in four years. DISCUSSION: This multicentre RCT will establish whether, for women of advanced age, women with ovulatory disease, and women who have a high risk for tubal pathology, there is a fertility enhancing effect of tubal flushing with oil-based contrast during HSG and whether the use of this contrast medium is cost-effective. Trial Registration The study was prospectively registered in the Netherlands Trial Register on August 1st 2019 as 'H2Oil2' (reference number NL7925, https://www.trialregister.nl/trial/7925 ).

Process evaluation of a multidisciplinary care program for patients undergoing gynaecological surgery.

PURPOSE: This study describes the process evaluation of an innovative multidisciplinary care program for patients undergoing benign gynaecologic surgery. This care program aims at improving recovery and preventing delayed return to work and consists of two steps: (1) an interactive e-health intervention for all participants, and (2) integrated clinical and occupational care management for those participants whose sick leave exceeds 10 weeks. METHODS: Eligible for this study were employed women aged between 18-65 years scheduled for a laparoscopic adnexal surgery and/or hysterectomy. Data were collected from patients, their supervisors and their gynaecologists, by means of electronic questionnaires during a 6 month follow-up period and an automatically generated, detailed weblog of the patient web portal ( www.ikherstel.nl ). Investigated process measures included: reach, dose delivered, dose received, and fidelity. In addition, attitudes towards the intervention were explored among all stakeholders. RESULTS: 215 patients enrolled in the study and accounted to a reach of 60.2 % (215/357). All intervention group patients used their account at least once and total time spent on the patient web portal was almost 2 h for each patient (median 118 min, IQR 64-173 min). Most patients visited the website several times (median 11 times, IQR 6-16). Perceived effectiveness among patients was high (74 %). In addition, gynaecologists (76 %) and employers (61 %) were satisfied with the web portal as well. Implementation of the second step of the intervention was suboptimal. Motivating patients to consent to additional guidance and developing an accurate return-to-work-prognosis were two important obstacles. CONCLUSIONS: The results of this study indicate good feasibility for implementation on a broad scale of the e-health intervention for patients undergoing benign gynaecological surgery. To enhance the implementation of the second step of the perioperative care program, adaptations in the integrated care protocol are needed.

Guideline adherence in ectopic pregnancy management.

BACKGROUND: Evidence-based guidelines have been issued for ectopic pregnancy (EP), covering both diagnostic and therapeutic management. In general, guidelines aim to reduce practice variation and to improve quality of care. To assess the guideline adherence in the management of EP, we developed guideline-based quality indicators and measured patient care in various hospitals. METHODS: A panel of experts and clinicians developed quality indicators based on recommendations from the Dutch guideline on EP management, using the systematic RAND-modified Delphi method. With these indicators, patient care was assessed in six Dutch hospitals between January 2003 and December 2005. For each quality indicator, a ratio for guideline adherence was calculated. Overall adherence was reported, as well as adherence per hospital type, i.e. academic, teaching and non-teaching hospitals. RESULTS: Out of 30 guideline-based recommendations, 12 quality indicators were selected covering procedural, structural and outcome aspects of care. For 317 women surgically treated for EP, these aspects were assessed. Overall adherence to the guideline was 75%. The highest adherence (98%) was observed for performing transvaginal sonography during the diagnostic workup. The lowest adherence (21%) was observed for performing salpingotomy in case of contra-lateral tubal pathology. Wide variance in adherence (0-100%) existed between academic, teaching and non-teaching hospitals. CONCLUSIONS: The overall guideline adherence was reasonable, with ample room for improvement in various aspects of care. Further research should focus on the barriers for guideline dissemination and adherence, to further improve the management of EP.

R56865 is antifibrillatory in reperfused ischemic guinea-pig hearts, even when given only during reperfusion.

R56865 was previously characterized as an inhibitor of Na and Ca overload that has beneficial effects during ischemia and reperfusion. An isolated guinea-pig heart preparation was subjected to 60 minutes of ischemia and 60 minutes of reperfusion. R56865 was given before ischemia and with the onset of reperfusion, applying different dosing schedules, including an initial loading dose. R56865 below 0.1 mumol/l had no cardiodepressant effects in normoxic hearts and at 0.1 mumol/l reduced left ventricular pressure marginally. The onset of ischemic contracture was delayed only at this concentration. R56865 given before ischemia potently inhibits delayed sustained fibrillation occurring during reperfusion in the concentration range between 0.01 mumol/l and 0.1 mumol/l. Analysis of cellular Na+, K+, and Ca2+ concentrations revealed that R56865 substantially improves the ionic homeostasis of myocardial cells. Most importantly, the compound also reduced the incidence of delayed sustained fibrillation when given at the onset of reperfusion. R56865 was most effective when fast equilibration of drug with tissue was achieved by giving an initial loading dose. In particular, the cellular Na+ and Ca2+ contents were improved using this dosing scheme. The results are compatible with the classification of R56865 as an inhibitor of Na+ and Ca2+ overload.

Enuresis treated by an improved waking apparatus.

One hundred and sixty children with enuresis were treated by the use of an improved waking apparatus which combines a buzzer and a battery-energized electrical stimulus. The over-all cure rate was 72%. Ninety-five patients were followed up for one year or more after treatment. When patients with organic, psychological and psychiatric problems were excluded the cure rate for the children with essential enuresis was 83%.