Water Management Solution of Reservoir Storage Function Under Condition of Measurement Uncertainties in Hydrological Input Data

AbstractThe paper describes a possible procedure of the rate uncertainty implementation to the continuous water stage measurement and uncertainties of state - discharge rating curve point positions, which the stage -discharge rating curves were fitted into the uncertainties of the real discharge series members. Then the members of discharge series under uncertainty impact were tested on the calculated values of the reservoir storage volume. The next step was the implementation of the uncertainties of the real discharge series members on the generation of the artificial discharge series of mean monthly discharge using the AR and ARMA generators and the determination of their impact on the calculated values of the reservoir storage volume

Risk of cancer in children and young adults conceived by assisted reproductive technology

STUDY QUESTION: Do children conceived by ART have an increased risk of cancer? SUMMARY ANSWER: Overall, ART-conceived children do not appear to have an increased risk of cancer. WHAT IS KNOWN ALREADY: Despite the increasing use of ART, i.e. IVF or ICSI worldwide, information about possible long-term health risks for children conceived by these techniques is scarce. STUDY DESIGN, SIZE, DURATION: A nationwide historical cohort study with prospective follow-up (median 21 years), including all live-born offspring from women treated with subfertility treatments between 1980 and 2001. PARTICIPANTS/MATERIALS, SETTING, METHODS: All offspring of a nationwide cohort of subfertile women (OMEGA study) treated in one of the 12 Dutch IVF clinics or two fertility clinics. Of 47 690 live-born children, 24 269 were ART-conceived, 13 761 naturally conceived and 9660 were conceived naturally or through fertility drugs, but not by ART. Information on the conception method of each child and potential confounders were collected through the mothers’ questionnaires and medical records. Cancer incidence was ascertained through linkage with The Netherlands Cancer Registry from 1 January 1989 until 1 November 2016. Cancer risk in ART-conceived children was compared with risks in naturally conceived children from subfertile women (hazard ratios [HRs]) and with the general population (standardized incidence ratios [SIRs]). MAIN RESULTS AND THE ROLE OF CHANCE: The median follow-up was 21 years (interquartile range (IQR): 17–25) and was shorter in ART-conceived children (20 years, IQR: 17–23) compared with naturally conceived children (24 years, IQR: 20–30). In total, 231 cancers were observed. Overall cancer risk was not increased in ART-conceived children, neither compared with naturally conceived children from subfertile women (HR: 1.00, 95% CI 0.72–1.38) nor compared with the general population (SIR = 1.11, 95% CI: 0.90–1.36). From 18 years of age onwards, the HR of cancer in ART-conceived versus naturally conceived individuals was 1.25 (95% CI: 0.73–2.13). Slightly but non-significantly increased risks were observed in children conceived by ICSI or cryopreservation (HR = 1.52, 95% CI: 0.81–2.85; 1.80, 95% CI: 0.65–4.95, respectively). Risks of lymphoblastic leukemia (HR = 2.44, 95% CI: 0.81–7.37) and melanoma (HR = 1.86, 95% CI: 0

Barriers and facilitators for the implementation of an online clinical health community in addition to usual fertility care: a cross-sectional study

Contains fulltext : 133059.pdf (publisher's version ) (Open Access)BACKGROUND: Online health communities are becoming more popular in health care. Patients and professionals can communicate with one another online, patients can find peer support, and professionals can use it as an additional information channel to their patients. However, the implementation of online health communities into daily practice is challenging. These challenges relate to the fact that patients need to be activated to (1) become a member (ie, subscription) and (2) participate actively within the community before any effect can be expected. Therefore, we aimed at answering 2 research questions: (1) what factors are associated with subscription to an online health community, and (2) which are associated with becoming an active participant within an online health community. OBJECTIVE: To identify barriers and facilitators as perceived by patients for the implementation of an online health community. METHODS: We performed a cross-sectional study. Three Dutch fertility clinics (2 IVF-licensed) offered their patients a secure online clinical health community through which clinicians can provide online information and patients can ask questions to the medical team or share experiences and find support from peers. We randomly selected and invited 278 men and women suffering from infertility and attending 1 of the participating clinics. Participants filled out a questionnaire about their background characteristics and current use of the online community. Possible barriers and facilitators were divided into 2 parts: (1) those for subscription to the community, and (2) those for active participation in the community. We performed 2 multivariate logistic regression analyses to calculate determinants for both subscription and active participation. RESULTS: Subscription appeared to be associated with patients' background characteristics (eg, gender, treatment phase), intervention-related facilitators (odds ratio [OR] 2.45, 95% CI 1.14-5.27), and patient-related barriers (OR 0.20, 95% CI 0.08-0.54), such as not feeling the need for such an online health community. After subscription, determinants for participation consisted of aspects related to participant's age (OR 0.86, 95% CI 0.76-0.97), length of infertility (OR 1.48, 05% CI 1.09-2.02), and to intervention-related facilitators (OR 5.79, 95% CI 2.40-13.98), such as its reliable character and possibility to interact with the medical team and peers. CONCLUSIONS: Implementing an online health community in addition to usual fertility care should be performed stepwise. At least 2 strategies are needed to increase the proportion of patient subscribers and consequently make them active participants. First, the marketing strategy should contain information tailored to different subgroups of the patient population. Second, for a living online health community, incorporation of interactive elements, as well as frequent news and updates are needed. These results imply that involving patients and their needs into the promotion strategy, community's design, and implementation are crucial

Antigen-specific active immunotherapy for ovarian cancer

Background Despite advances in chemotherapy, prognosis of ovarian cancer remains poor. Antigen-specific active immunotherapy aims to induce a tumour-antigen-specific anti-tumour immune responses as an alternative treatment for ovarian cancer. Objectives To assess feasibility of antigen-specific active immunotherapy for ovarian cancer. Primary outcomes are clinical efficacy and antigen-specific immunogenicity with carrier-specific immunogenicity and side-effects as secondary outcomes. Search strategy A systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 3, 2009, Cochrane Gynaecological Cancer Group Specialized Register, MEDLINE and EMBASE databases and clinicaltrials.gov was performed (1966 to July 2009). Hand searches were conducted of the proceedings of relevant annual meetings (1996 to July 2009). Selection criteria Randomised controlled trials (RCTs), as well as non-randomised non-controlled studies that included patients with epithelial ovarian cancer, irrespective of stage of disease, and treated with antigen-specific active immunotherapy, irrespective of type of vaccine, antigen used, adjuvant used, route of vaccination, schedule, and reported clinical or immunological outcomes. Data collection and analysis Data extraction was performed independently by two review authors. Risk of bias was evaluated with the Delphi-list for RCTs or a selection of quality domains pivotal to the assessment of non-RCTs and deemed best applicable to the non-randomised non-controlled studies. Main results Thirty-six studies were included. Response definitions showed substantial variation between trials, which makes comparison of trial results unreliable. Information on adverse events was frequently limited. Furthermore, reports of both RCTs and non-RCTs frequently lacked information necessary to assess risk of bias. Serious biases in these trials can thus not be ruled out. The largest body of evidence is currently available for CA-125 targeted antibody therapy (15 studies: 1505 patients). Non-RCTs of this CA-125 targeted antibody therapy suggest increased survival in humoral and/ or cellular responders. However, three large randomised placebo-controlled trials did not show any clinical benefit despite induction of immune responses in approximately 60% of patients. Other small studies targeting many different tumour antigens showed promising immunological results. As these strategies have not yet been tested in RCTs, no reliable inferences about clinical efficacy can be made. Given the promising immunological results, limited side effects and toxicity exploration of clinical efficacy in large well-designed RCTs may be worthwhile. Authors' conclusions We conclude that despite promising immunological responses no clinically effective antigen-specific active immunotherapy is yet available for ovarian cancer. Furthermore, the adoption of guidelines to ensure uniformity in trial conduct, response definitions and trial reporting is recommended to improve quality and comparability of immunotherapy trials

A randomized clinical trial of clomiphene citrate versus low dose recombinant FSH for ovarian hyperstimulation in intrauterine insemination cycles for unexplained and male subfertility.

Contains fulltext : 51782.pdf (publisher's version ) (Closed access)BACKGROUND: Controlled ovarian hyperstimulation with intrauterine insemination (IUI) is a widely accepted treatment for unexplained and male subfertility. No consensus exists about the drug of first choice to be used as hyperstimulation. This randomized multicentre trial using a parallel design compares the efficacy of clomiphene citrate (CC) with that of recombinant FSH (rFSH). METHODS: Couples with primary unexplained or male subfertility were randomized to receive CC or rFSH for ovarian hyperstimulation. The treatment was continued for up to four cycles unless pregnancy occurred. Cycles with more than three follicles were cancelled. Cumulative pregnancy rates and live birth rates were primary outcomes. Cancellation during treatment and multiple birth rates are secondary outcomes. Results were analysed following the intention-to-treat principle. RESULTS: Seventy couples with male subfertility and 68 couples with unexplained subfertility were included. Seventy-one women received CC, and 67 received rFSH. Twenty-seven pregnancies were observed in the CC group (38%) and 23 in the rFSH group (34.3%) relative risk (RR) 1.11 [95% confidence interval (95% CI) 0.71-1.73]. The live birth rate was 28.2% (20/71) and 26.9% (18/67) for CC and rFSH, respectively, RR 1.05 (95% CI 0.61-1.80). Overall, the live birth rates per cycle were 10% for CC-stimulated and 8.7% for rFSH stimulated cycles. The total multiple pregnancy rate was 6.0%. Thirty-five cycles (8.6%) were cancelled because of four or more follicles (CC, n = 17; rFSH, n = 18). CONCLUSIONS: In couples with primary unexplained or male subfertility participating in an IUI program, ovarian hyperstimulation can be achieved by CC or rFSH. No significant difference in live birth rates between CC and rFSH was observed. Being less expensive, CC seems the more cost-effective drug and therefore, can be offered as drug of first choice

Communication at an online infertility expert forum: provider responses to patient's emotional and informational cues.

Online patient-provider communication has become increasingly popular in fertility care. However, it is not known to what extent patients express cues or concerns and how providers respond. In this study, we investigated cues and responses that occur in online patient-provider communication at an infertility-specific expert forum. We extracted 106 threads from the multidisciplinary expert forum of two Dutch IVF clinics. We performed the following analyses: (1) thematic analysis of patients’ questions; and (2) rating patients’ emotional and informational cues and subsequent professionals’ responses using an adaptation of the validated Medical Interview Aural Rating Scale. Frequencies of themes, frequencies of cues and responses, and sequences (what cue is followed by what response) were extracted. Sixty-five infertile patients and 19 providers participated. The most common themes included medication and lifestyle. Patients gave more informational than emotional cues (106 versus 64). Responses to informational cues were mostly adequate (61%). The most common response to emotional cues was empathic acknowledgment (72%). Results indicate that an online expert forum could have a positive effect on patient outcomes, which should guide future research. Offering infertile patients an expert forum to communicate with providers can be a promising supplement to usual care in both providing information and addressing patients’ concerns. (aut. ref.

[Ten years of results of in-vitro fertilisation in the Netherlands 1996-2005]

Item does not contain fulltextOBJECTIVE: To present the numbers and results of Dutch IVF treatment from 1996-2005 and to describe trends and differences between centres. DESIGN: Retrospective data-collection, description and analysis. METHOD: The annual statistics from all Dutch IVF centres covering the years 1996-2005 were collected, described and analysed. RESULTS: During this period 138,217 IVF or intracytoplasmic sperm injection (ICSI) cycles were started and 14,881 transfers of frozen-thawed embryos (cryo transfers) were performed. The number of ICSI treatments, in particular, increased to more than 6000 cycles during this period. These treatments resulted in 30,488 ongoing pregnancies (22.1% per cycle started; 19.1% for IVF and 23.4% for ICSI). The ongoing pregnancy rate per cycle increased from 17.6% in 1996 to 24.4% in 2005. The increase after cryo transfers was remarkable (from 9.4% to 17.6%). It is estimated that during this period, about 1 in 52 newborns in the Netherlands was an IVF or ICSI child (1996: 1 in 77, 2005: 1 in 43). There were differences between the individual centres regarding the ongoing pregnancy rate per cycle (range: 15.0-26.4%), the percentage of ICSI (range 20-58%), the percentage of cryo transfers per cycle (range: 4-22%) and the multiple pregnancy rate (range 5-27% in 2005). CONCLUSIONS: In the Netherlands the pregnancy rate has increased over the last 10 years as has the number of IVF treatments. Cryo transfers have become increasingly important and the multiple pregnancy rate has decreased. Although thanks to the collaboration of all centres, the current registry produces important data and works well, there are a number of limitations e.g. the retrospective nature with no validation, which must be tackled over the coming years

Ovarian stimulation strategies for intrauterine insemination in couples with unexplained infertility: a systematic review and individual participant data meta-analysis

Advance Access Publication on May 18, 2022BACKGROUND: Intrauterine insemination with ovarian stimulation (IUI-OS) is a first-line treatment for unexplained infertility. Gonadotrophins, letrozole and clomiphene citrate (CC) are commonly used agents during IUI-OS and have been compared in multiple aggregate data meta-analyses, with substantial heterogeneity and no analysis on time-to-event outcomes. Individual participant data metaanalysis (IPD-MA) is considered the gold standard for evidence synthesis as it can offset inadequate reporting of individual studies by obtaining the IPD, and allows analyses on treatment–covariate interactions to identify couples who benefit most from a particular treatment. OBJECTIVE AND RATIONALE: We performed this IPD-MA to compare the effectiveness and safety of ovarian stimulation with gonadotrophins, letrozole and CC and to explore treatment–covariate interactions for important baseline characteristics in couples undergoing IUI. SEARCH METHODS: We searched electronic databases including MEDLINE, EMBASE, CENTRAL, CINAHL, and PsycINFO from their inception to 28 June 2021. We included randomized controlled trials (RCTs) comparing IUI-OS with gonadotrophins, letrozole and CC among couples with unexplained infertility. We contacted the authors of eligible RCTs to share the IPD and established the IUI IPD-MA Collaboration. The primary effectiveness outcome was live birth and the primary safety outcome was multiple pregnancy. Secondary outcomes were other reproductive outcomes, including time to conception leading to live birth. We performed a one-stage random effects IPD-MA. OUTCOMES: Seven of 22 (31.8%) eligible RCTs provided IPD of 2495 couples (62.4% of the 3997 couples participating in 22 RCTs), of which 2411 had unexplained infertility and were included in this IPD-MA. Six RCTs (n¼1511) compared gonadotrophins with CC, and one (n¼900) compared gonadotrophins, letrozole and CC. Moderate-certainty evidence showed that gonadotrophins increased the live birth rate compared to CC (6 RCTs, 2058 women, RR 1.30, 95% CI 1.12–1.51, I2 ¼ 26%). Low-certainty evidence showed that gonadotrophins may also increase the multiple pregnancy rate compared to CC (6 RCTs, 2058 women, RR 2.17, 95% CI 1.33–3.54, I2 ¼ 69%). Heterogeneity on multiple pregnancy could be explained by differences in gonadotrophin starting dose and choice of cancellation criteria. Post-hoc sensitivity analysis on RCTs with a low starting dose of gonadotrophins (<75 IU) confirmed increased live birth rates compared to CC (5 RCTs, 1457 women, RR 1.26, 95% CI 1.05–1.51), but analysis on only RCTs with stricter cancellation criteria showed inconclusive evidence on live birth (4 RCTs, 1238 women, RR 1.15, 95% CI 0.94–1.41). For multiple pregnancy, both sensitivity analyses showed inconclusive findings between gonadotrophins and CC (RR 0.94, 95% CI 0.45–1.96; RR 0.81, 95% CI 0.32–2.03, respectively). Moderate certainty evidence showed that gonadotrophins reduced the time to conception leading to a live birth when compared to CC (6 RCTs, 2058 women, HR 1.37, 95% CI 1.15–1.63, I2 ¼ 22%). No strong evidence on the treatment–covariate (female age, BMI or primary versus secondary infertility) interactions was found. WIDER IMPLICATIONS: In couples with unexplained infertility undergoing IUI-OS, gonadotrophins increased the chance of a live birth and reduced the time to conception compared to CC, at the cost of a higher multiple pregnancy rate, when not differentiating strategies on cancellation criteria or the starting dose. The treatment effects did not seem to differ in women of different age, BMI or primary versus secondary infertility. In a modern practice where a lower starting dose and stricter cancellation criteria are in place, effectiveness and safety of different agents seem both acceptable, and therefore intervention availability, cost and patients’ preferences should factor in the clinical decision-making. As the evidence for comparisons to letrozole is based on one RCT providing IPD, further RCTs comparing letrozole and other interventions for unexplained infertility are needed.J.A. Wessel, N.A. Danhof, R. van Eekelen, M.P. Diamond, R.S. Legro, K. Peeraer, T.M. D, Hooghe, M. Erdem, T. Dankert, B.J. Cohlen, C. Thyagaraju, B.W.J. Mol, M. Showell, M. van Wely, M.H. Mochtar, and R. Wan